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1. Longitudinal analyses of cerebrospinal fluid α‐Synuclein in prodromal and early Parkinson's disease

Author

Mollenhauer, Brit, Caspell‐Garcia, Chelsea J, Coffey, Christopher S, Taylor, Peggy, Singleton, Andy, Shaw, Leslie M, Trojanowski, John Q, Frasier, Mark, Simuni, Tanya, Iranzo, Alex, Oertel, Wolfgang, Siderowf, Andrew, Weintraub, Daniel, Seibyl, John, Toga, Arthur W, Tanner, Caroline M, Kieburtz, Karl, Chahine, Lana M, Marek, Kenneth, Galasko, Douglas, and study, for the PPMI

Subjects
Brain Disorders, Clinical Research, Parkinson's Disease, Aging, Neurodegenerative, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Neurological, Adult, Age of Onset, Aged, Aged, 80 and over, Biomarkers, Cohort Studies, Female, Genetic Variation, Humans, Longitudinal Studies, Male, Middle Aged, Negative Results, Olfaction Disorders, Parkinson Disease, Prodromal Symptoms, Prospective Studies, Psychiatric Status Rating Scales, REM Sleep Behavior Disorder, Tomography, Emission-Computed, Single-Photon, alpha-Synuclein, cohort studies, outcome research, Parkinson's disease, parkinsonism, PPMI study, Parkinson's disease/parkinsonism, Clinical Sciences, Human Movement and Sports Sciences, Neurology & Neurosurgery
Abstract

BackgroundAggregation of α-synuclein is central to the pathophysiology of PD. Biomarkers related to α-synuclein may be informative for PD diagnosis/progression.ObjectivesTo analyze α-synuclein in CSF in drug-naïve PD, healthy controls, and prodromal PD in the Parkinson's Progression Markers Initiative.MethodsOver up to 36-month follow-up, CSF total α-synuclein and its association with MDS-UPDRS motor scores, cognitive assessments, and dopamine transporter imaging were assessed.ResultsThe inception cohort included PD (n = 376; age [mean {standard deviation} years]: 61.7 [9.62]), healthy controls (n = 173; age, 60.9 [11.3]), hyposmics (n = 16; age, 68.3 [6.15]), and idiopathic rapid eye movement sleep behavior disorder (n = 32; age, 69.3 [4.83]). Baseline CSF α-synuclein was lower in manifest and prodromal PD versus healthy controls. Longitudinal α-synuclein decreased significantly in PD at 24 and 36 months, did not change in prodromal PD over 12 months, and trended toward an increase in healthy controls. The decrease in PD was not shown when CSF samples with high hemoglobin concentration were removed from the analysis. CSF α-synuclein changes did not correlate with longitudinal MDS-UPDRS motor scores or dopamine transporter scan.ConclusionsCSF α-synuclein decreases early in the disease, preceding motor PD. CSF α-synuclein does not correlate with progression and therefore does not reflect ongoing dopaminergic neurodegeneration. Decreased CSF α-synuclein may be an indirect index of changes in the balance between α-synuclein secretion, solubility, or aggregation in the brain, reflecting its overall turnover. Additional biomarkers more directly related to α-synuclein pathophysiology and disease progression and other markers to be identified by, for example, proteomics and metabolomics are needed. © 2019 International Parkinson and Movement Disorder Society.

Published
2019

2. Cerebrospinal fluid, plasma, and saliva in the BioFIND study: Relationships among biomarkers and Parkinson's disease Features

Author

Goldman, Jennifer G, Andrews, Howard, Amara, Amy, Naito, Anna, Alcalay, Roy N, Shaw, Leslie M, Taylor, Peggy, Xie, Tao, Tuite, Paul, Henchcliffe, Claire, Hogarth, Penelope, Frank, Samuel, Saint‐Hilaire, Marie‐Helene, Frasier, Mark, Arnedo, Vanessa, Reimer, Alyssa N, Sutherland, Margaret, Swanson‐Fischer, Christine, Gwinn, Katrina, Discovery, The Fox Investigation of New Biomarker, and Kang, Un Jung

Subjects
Parkinson's Disease, Clinical Research, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Acquired Cognitive Impairment, Aging, Neurodegenerative, Dementia, Aetiology, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, 2.1 Biological and endogenous factors, Neurological, Aged, Amyloid beta-Peptides, Biomarkers, Cohort Studies, Correlation of Data, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Parkinson Disease, Peptide Fragments, Postural Balance, Saliva, Sensation Disorders, United States, alpha-Synuclein, tau Proteins, Fox Investigation of New Biomarker Discovery, alpha-synuclein, amyloid, cerebrospinal fluid, postural instability gait difficulty, tau, Clinical Sciences, Human Movement and Sports Sciences, Neurology & Neurosurgery
Abstract

ObjectiveExamine relationships among neurodegenerative biomarkers and PD motor and nonmotor symptoms.BackgroundCSF alpha-synuclein is decreased in PD versus healthy controls, but whether plasma and saliva alpha-synuclein differentiate these groups is controversial. Correlations of alpha-synuclein among biofluids (CSF, plasma, saliva) or biomarkers (eg, beta-amyloid, tau [total, phosphorylated]) are not fully understood. The relationships of these biomarkers with PD clinical features remain unclear.MethodsBioFIND, a cross-sectional, observational study, examines clinical and biomarker characteristics in moderate-advanced PD and matched healthy controls. We compared alpha-synuclein concentrations across diagnosis, biofluids, and CSF biomarkers. Correlations of CSF biomarkers and MDS-UPDRS, motor phenotype, MoCA, and rapid eye movement sleep behavior disorder questionnaire scores in PD were examined.ResultsCSF alpha-synuclein was lower in PD versus controls (P = .01), controlling for age, gender, and education. Plasma and saliva alpha-synuclein did not differ between PD and controls, and alpha-synuclein did not significantly correlate among biofluids. CSF beta-amyloid1-42 was lower in PD versus controls (P

Published
2018

3. Age-associated insolubility of parkin in human midbrain is linked to redox balance and sequestration of reactive dopamine metabolites

Author

Tokarew, Jacqueline M., El-Kodsi, Daniel N., Lengacher, Nathalie A., Fehr, Travis K., Nguyen, Angela P., Shutinoski, Bojan, O’Nuallain, Brian, Jin, Ming, Khan, Jasmine M., Ng, Andy C. H., Li, Juan, Jiang, Qiubo, Zhang, Mei, Wang, Liqun, Sengupta, Rajib, Barber, Kathryn R., Tran, An, Im, Doo Soon, Callaghan, Steve, Park, David S., Zandee, Stephanie, Dong, Xiajun, Scherzer, Clemens R., Prat, Alexandre, Tsai, Eve C., Takanashi, Masashi, Hattori, Nobutaka, Chan, Jennifer A., Zecca, Luigi, West, Andrew B., Holmgren, Arne, Puente, Lawrence, Shaw, Gary S., Toth, Gergely, Woulfe, John M., Taylor, Peggy, Tomlinson, Julianna J., and Schlossmacher, Michael G.

Published
2021
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4. Clinical and dopamine transporter imaging characteristics of non-manifest LRRK2 and GBA mutation carriers in the Parkinson's Progression Markers Initiative (PPMI): a cross-sectional study

Author

Arnedo, Vanessa, Clark, Adrienne, Fraiser, Mark, Kopil, Catherine, Chowdhury, Sohini, Sherer, Todd, Daegele, Nichole, Casaceli, Cynthia, Dorsey, Ray, Wilson, Renee, Mahes, Sugi, Salerno, Christina, Crawford, Karen, Casalin, Paola, Malferrari, Giulia, Weisz, Mali Gani, Orr-Urtreger, Avi, Montine, Thomas, Baglieri, Chris, Christini, Amanda, Russell, David, Dahodwala, Nabila, Giladi, Nir, Factor, Stewart, Hogarth, Penelope, Standaert, David, Hauser, Robert, Jankovic, Joseph, Saint-Hilaire, Marie, Richard, Irene, Shprecher, David, Fernandez, Hubert, Brockmann, Katrina, Rosenthal, Liana, Barone, Paolo, Espay, Alberto, Rowe, Dominic, Marder, Karen, Santiago, Anthony, Hu, Shu-Ching, Isaacson, Stuart, Corvol, Jean-Christophe, Ruiz Martinez, Javiar, Tolosa, Eduardo, Tai, Yen, Politis, Marios, Smejdir, Debra, Rees, Linda, Williams, Karen, Kausar, Farah, Richardson, Whitney, Willeke, Diana, Peacock, Shawnees, Sommerfeld, Barbara, Freed, Alison, Wakeman, Katrina, Blair, Courtney, Guthrie, Stephanie, Harrell, Leigh, Hunter, Christine, Thomas, Cathi-Ann, James, Raymond, Zimmerman, Grace, Brown, Victoria, Mule, Jennifer, Hilt, Ella, Ribb, Kori, Ainscough, Susan, Wethington, Misty, Ranola, Madelaine, Mejia Santana, Helen, Moreno, Juliana, Raymond, Deborah, Speketer, Krista, Carvajal, Lisbeth, Carvalo, Stephanie, Croitoru, Ioana, Garrido, Alicia, Payne, Laura Marie, Viswanth, Veena, Severt, Lawrence, Facheris, Maurizio, Soares, Holly, Mintun, Mark A., Cedarbaum, Jesse, Taylor, Peggy, Biglan, Kevin, Vandenbroucke, Emily, Haider Sheikh, Zulfiqar, Bingol, Baris, Fischer, Tanya, Sardi, Pablo, Forrat, Remi, Reith, Alastair, Egebjerg, Jan, Ahlberg Hillert, Gabrielle, Saba, Barbara, Min, Chris, Umek, Robert, Mather, Joe, De Santi, Susan, Post, Anke, Boess, Frank, Taylor, Kirsten, Grachev, Igor, Avbersek, Andreja, Muglia, Pierandrea, Merchant, Kaplana, Tauscher, Johannes, Simuni, Tanya, Uribe, Liz, Cho, Hyunkeun Ryan, Caspell-Garcia, Chelsea, Coffey, Christopher S, Siderowf, Andrew, Trojanowski, John Q, Shaw, Leslie M, Seibyl, John, Singleton, Andrew, Toga, Arthur W, Galasko, Doug, Foroud, Tatiana, Tosun, Duygu, Poston, Kathleen, Weintraub, Daniel, Mollenhauer, Brit, Tanner, Caroline M, Kieburtz, Karl, Chahine, Lana M, Reimer, Alyssa, Hutten, Samantha J, Bressman, Susan, and Marek, Kenneth

Published
2020
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5. CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study

Author

Kang, Ju-Hee, Mollenhauer, Brit, Coffey, Christopher S, Toledo, Jon B, Weintraub, Daniel, Galasko, Douglas R, Irwin, David J, Van Deerlin, Vivianna, Chen-Plotkin, Alice S, Caspell-Garcia, Chelsea, Waligórska, Teresa, Taylor, Peggy, Shah, Nirali, Pan, Sarah, Zero, Pawel, Frasier, Mark, Marek, Kenneth, Kieburtz, Karl, Jennings, Danna, Tanner, Caroline M, Simuni, Tanya, Singleton, Andrew, Toga, Arthur W, Chowdhury, Sohini, Trojanowski, John Q, Shaw, Leslie M, and The Parkinson’s Progression Marker Initiative

Subjects
Biomedical and Clinical Sciences, Neurosciences, Prevention, Parkinson's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Aging, Neurodegenerative, Clinical Research, Alzheimer's Disease, Brain Disorders, Acquired Cognitive Impairment, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Aetiology, 4.2 Evaluation of markers and technologies, Neurological, Adult, Aged, Aged, 80 and over, Amyloid beta-Peptides, Biomarkers, Cognition, Cognition Disorders, Disease Progression, Early Diagnosis, Female, Humans, Male, Middle Aged, Parkinson Disease, Peptide Fragments, Phenotype, Prospective Studies, Parkinson's disease, Cerebrospinal fluid biomarker, Parkinson's Progression Markers Initiative, A beta(1-42), Tau, Alpha-synuclein, Parkinson’s Progression Marker Initiative, Aβ1-42, Parkinson’s Progression Markers Initiative, Parkinson’s disease, Clinical Sciences, Neurology & Neurosurgery
Abstract

The development of biomarkers to predict the progression of Parkinson's disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson's Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1-42 (Aβ1-42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1-42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1-42, or highest t-tau/Aβ1-42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1-42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance.

Published
2016

6. In vivo distribution of α-synuclein in multiple tissues and biofluids in Parkinson disease

Author

Chahine, Lana M., Beach, Thomas G., Brumm, Michael C., Adler, Charles H., Coffey, Christopher S., Mosovsky, Sherri, Caspell-Garcia, Chelsea, Serrano, Geidy E., Munoz, David G., White, Charles L., III, Crary, John F., Jennings, Danna, Taylor, Peggy, Foroud, Tatiana, Arnedo, Vanessa, Kopil, Catherine M., Riley, Lindsey, Dave, Kuldip D., and Mollenhauer, Brit

Published
2020
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7. Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study

Author

Kruse, Niels, Persson, Staffan, Alcolea, Daniel, Bahl, Justyna M.C., Baldeiras, Ines, Capello, Elisabetta, Chiasserini, Davide, Bocchio Chiavetto, Luisella, Emersic, Andreja, Engelborghs, Sebastiaan, Eren, Erden, Fladby, Tormod, Frisoni, Giovanni, García-Ayllón, María-Salud, Genc, Sermin, Gkatzima, Olymbia, Heegaard, Niels H.H., Janeiro, André M., Kováčech, Branislav, Kuiperij, H. Bea, Leitão, Maria J., Lleó, Alberto, Martins, Madalena, Matos, Mafalda, Mollergard, Hanne M., Nobili, Flavio, Öhrfelt, Annika, Parnetti, Lucilla, de Oliveira, Catarina Resende, Rot, Uros, Sáez-Valero, Javier, Struyfs, Hanne, Tanassi, Julia T., Taylor, Peggy, Tsolaki, Magda, Vanmechelen, Eugeen, Verbeek, Marcel M., Zilka, Norbert, Blennow, Kaj, Zetterberg, Henrik, and Mollenhauer, Brit

Published
2015
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10. The genetic architecture of the human cerebral cortex

Author

Grasby, Katrina L, Jahanshad, Neda, Shatokhina, Natalia, Mirza-Schreiber, Nazanin, Moreira, Jose C V, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M, Orfanos, Dimitri Papadopoulos, Pearson, John F, Zsembik, Leo C P, Pitcher, Toni L, Pütz, Benno, Quidé, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M, Reay, William R, Redlich, Ronny, Reinbold, Céline S, Repple, Jonathan, Richard, Geneviève, Thomopoulos, Sophia I, Riedel, Brandalyn C, Risacher, Shannon L, Rocha, Cristiane S, Mota, Nina Roth, Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J, Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R, Zhu, Alyssa H, Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E, Sprooten, Emma, Tansey, Katherine E, Teumer, Alexander, Thalamuthu, Anbupalam, Strike, Lachlan T, Tordesillas-Gutiérrez, Diana, Turner, Jessica A, Uhlmann, Anne, Vallerga, Costanza Ludovica, van der Meer, Dennis, van Donkelaar, Marjolein M J, van Eijk, Liza, van Erp, Theo G M, van Haren, Neeltje E M, van Rooij, Daan, Agartz, Ingrid, van Tol, Marie-José, Veldink, Jan H, Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M, Wen, Wei, Westlye, Lars T, Whelan, Christopher D, Alhusaini, Saud, Witt, Stephanie H, Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L, Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P, Artiges, Eric, Almeida, Marcio A A, Assareh, Amelia A, Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L, Brown, Gregory G, Cichon, Sven, Curran, Joanne E, Davies, Gareth E, Degenhardt, Franziska, Dennis, Michelle F, Alnæs, Dag, Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P, Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A, Green, Robert C, Häusler, Alexander N, Heindel, Walter, Amlien, Inge K, Ho, Beng-Choon, Hoffmann, Wolfgang U, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R, Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A, Kolskår, Knut, Painter, Jodie N, Andersson, Micael, Koops, Sanne, Krug, Axel, Lim, Kelvin O, Luykx, Jurjen J, Mathalon, Daniel H, Mather, Karen A, Mattay, Venkata S, Matthews, Sarah, Mayoral Van Son, Jaqueline, McEwen, Sarah C, Ard, Tyler, Melle, Ingrid, Morris, Derek W, Mueller, Bryon A, Nauck, Matthias, Nordvik, Jan E, Nöthen, Markus M, O'Leary, Daniel S, Opel, Nils, Martinot, Marie-Laure Paillère, Pike, G Bruce, Armstrong, Nicola J, Preda, Adrian, Quinlan, Erin B, Rasser, Paul E, Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M, Tooney, Paul A, Torres, Fábio R, Veltman, Dick J, Voyvodic, James T, Ashley-Koch, Allison, Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H H, Bis, Joshua C, Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Atkins, Joshua R, Ikram, M Arfan, Launer, Lenore, Longstreth, W. T., Lopez, Oscar L, Mazoyer, Bernard, Mosley, Thomas H, Roshchupkin, Gennady V, Satizabal, Claudia L, Schmidt, Reinhold, Seshadri, Sudha, Bernard, Manon, Yang, Qiong, Initiative, Alzheimer’s Disease Neuroimaging, Consortium, CHARGE, Consortium, EPIGEN, Consortium, IMAGEN, Consortium, SYS, Initiative, Parkinson’s Progression Markers, Alvim, Marina K M, Ames, David, Anderson, Tim J, Brouwer, Rachel M, Andreassen, Ole A, Arias-Vasquez, Alejandro, Bastin, Mark E, Baune, Bernhard T, Beckham, Jean C, Blangero, John, Boomsma, Dorret I, Brodaty, Henry, Brunner, Han G, Buckner, Randy L, Buimer, Elizabeth E L, Buitelaar, Jan K, Bustillo, Juan R, Cahn, Wiepke, Cairns, Murray J, Calhoun, Vince, Carr, Vaughan J, Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L, Cendes, Fernando, Bülow, Robin, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C, Dannlowski, Udo, de Geus, Eco J C, Deary, Ian J, Delanty, Norman, Depondt, Chantal, Desrivières, Sylvane, Donohoe, Gary, Bürger, Christian, Espeseth, Thomas, Fernández, Guillén, Fisher, Simon E, Flor, Herta, Forstner, Andreas J, Francks, Clyde, Franke, Barbara, Glahn, David C, Gollub, Randy L, Grabe, Hans J, Colodro-Conde, Lucía, Cannon, Dara M, Gruber, Oliver, Håberg, Asta K, Hariri, Ahmad R, Hartman, Catharina A, Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans A, Hillegers, Manon H J, Hoekstra, Pieter J, Holmes, Avram J, Chakravarty, Mallar, Hong, L Elliot, Hopkins, William D, Hulshoff Pol, Hilleke E, Jernigan, Terry L, Jönsson, Erik G, Kahn, René S, Kennedy, Martin A, Kircher, Tilo T J, Kochunov, Peter, Kwok, John B J, Chen, Qiang, Le Hellard, Stephanie, Loughland, Carmel M, Martin, Nicholas G, Martinot, Jean-Luc, McDonald, Colm, McMahon, Katie L, Meyer-Lindenberg, Andreas, Michie, Patricia T, Morey, Rajendra A, Mowry, Bryan, Cheung, Joshua W, Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A, Pantelis, Christos, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Polderman, Tinca J C, Posthuma, Danielle, Rietschel, Marcella, Couvy-Duchesne, Baptiste, Roffman, Joshua L, Rowland, Laura M, Sachdev, Perminder S, Sämann, Philipp G, Schall, Ulrich, Schumann, Gunter, Scott, Rodney J, Sim, Kang, Sisodiya, Sanjay M, Smoller, Jordan W, Dale, Anders M, Sommer, Iris E, St Pourcain, Beate, Stein, Dan J, Toga, Arthur W, Trollor, Julian N, Van der Wee, Nic J A, van 't Ent, Dennis, Völzke, Henry, Walter, Henrik, Weber, Bernd, Dalvie, Shareefa, Weinberger, Daniel R, Wright, Margaret J, Zhou, Juan, Stein, Jason L, Thompson, Paul M, Medland, Sarah E, Consortium, Enhancing NeuroImaging Genetics through Meta-Analysis, Witte, A Veronica, Darin, Abigail, Fleisher, Adam, de Araujo, Tânia K, Pierce, Aimee, Mintz, Akiva, Lerner, Alan, Reith, Alastair D, Hofman, Albert, Espay, Alberto, Ihlenfeld, Albrecht, Ing, Alex, Iranzo, Alex, Beiser, Alexa S, de Zubicaray, Greig I, Norbash, Alexander, Barbot, Alexis, Rudolph, Alice, Portillo, Alicia, Chalker, Alison, Levey, Allan I, Rosen, Allyson, Smith, Amanda, Catafau, Ana, de Zwarte, Sonja M C, Ulysse, Anaztasia, Uitterlinden, André G, Becker, Andreas, Budson, Andrew E, Kertesz, Andrew, Siderowf, Andrew, Bralten, Janita, den Braber, Anouk, Singleton, Andrew, James, Angela, Oliver, Angela, Mishra, Aniket, Hake, Ann Marie, Burke, Anna, Sarrael, Antero, Porsteinsson, Anton P, Stringaris, Argyris, McCoy, Arita, Doan, Nhat Trung, Villringer, Arno, Lenahan, Art, Toga, Arthur, Bokde, Arun, Rawlins, Ashlee, Lamb, Ashley, Lee, Athena, Raj, Balebail Ashok, Tran, Baochan, Dohm, Katharina, Ruggeri, Barbara, Saba, Barbara, Lane, Barton, Yanez, Beatriz, Ances, Beau, Dunlop, Becky, Mudge, Benita, Ravina, Bernard, Ittermann, Bernd, Ehrlich, Stefan, van Noort, Betteke, Lind, Betty, Shah, Bina, Stefanovic, Bojana, Goldstein, Bonnie S, Bonakdarpour, Borna, Matthews, Brandy R, Borowski, Bret, Ott, Brian R, Reynolds, Brigid, Engelbrecht, Hannah-Ruth, Mollenhauer, Brit, Miller, Bruce L, Psaty, Bruce M, Spann, Bryan M, Sadowsky, Carl, Linder, Carly, Franz, Carol E, Tanner, Caroline, Kopil, Catherine, Thomas, Cathi-Ann, Erk, Susanne, Ward, Chad, Bernick, Charles, Smith, Charles D, DeCarli, Charles, Caspell, Chelsea, Deeley, Cheryl, Riordan, Cheryl, Mathis, Chet, Onyike, Chiadi, Heyn, Chris Chinthaka, Fan, Chun Chieh, Hosein, Chris, Leach, Christi, Bÿchel, Christian, Gigliotti, Christina, Hunter, Christine, Belden, Christine M, Tzourio, Christophe, Coffey, Christopher, van Dyck, Christopher H, Clark, Christopher M, Fedko, Iryna O, Wu, Chuang-Kuo, Albers, Colleen S, Chu, Congying, Brand, Connie, Isensee, Corinna, van Duijn, Cornelia M, Bishop, Courtney, Bodge, Courtney, Foley, Sonya F, Tatsuoka, Curtis, Casaceli, Cynthia, Carlsson, Cynthia M, Mathews, Dana, D'Agostino, Daniel, Silverman, Daniel H S, Marson, Daniel, Berg, Daniela, Harvey, Danielle, Jennings, Danna, Ford, Judith M, Wolk, David A, Goldstein, David B, Bachman, David, Brooks, David, Clark, David, Geldmacher, David, Hart, David, Holtzman, David, Jones, David, Hibar, Derrek P, Fukunaga, Masaki, Knopman, David, Hewitt, David L, Perry, David, Russell, David, Standaert, David, Winkfield, David, Green, Davis Robert C, Fontaine, Deborah, Miller, Delwyn D, Gessert, Devon, Garrett, Melanie E, Kerwin, Diana, Willeke, Diana, Drost, Dick, Papadopoulos, Dimitri, Rowe, Dominic, Simpson, Donna M, Muni, Donna, Galasko, Douglas, Scharre, Douglas W, Fillmer, Ariane, Ge, Tian, Bartha, Rob, Celmins, Dzintra, Zimmerman, Earl A, Teng, Edmond, Tolosa, Eduardo, Coleman, Edward, Zamrini, Edward, Mitsis, Effie, Finger, Elizabeth, Giddaluru, Sudheer, Oates, Elizabeth, Sosa, Elizabeth, Woo, Ellen, Rogalski, Emily, Lethbridge, Emma, Dooley, Eoin, Foster, Eric, Reiman, Eric M, Quinlan, Erin Burke, Goldman, Aaron L, Franklin, Erin, Heinzen, Erin L, Fletcher, Evan, Sprenger, Fabienne, Crivello, Fabrice, Biondo, Francesca, Parfitt, Francine, Hefti, Franz, Beyer, Frauke, Nees, Frauke, Green, Melissa J, Leonard, Gabriel, Robert, Gabriel, Thai, Gaby, Marshall, Gad A, Barker, Gareth, Conrad, Gary, Tremont, Geoffrey, Bartzokis, George, Groenewold, Nynke A, Hsiung, Ging-Yuek Robin, Malferrari, Giulia, Chiang, Gloria, Pearlson, Godfrey D, Liang, Grace, Jicha, Greg, Sorensen, Greg, Todd, Gretchen, Jimenez, Gustavo, Grotegerd, Dominik, Zare, Habil, Grabe, Hans Jörgen, Vanderswag, Helen, Schmidt, Helena, Venkov, Heli, Lemaitre, Hervé, Gurholt, Tiril P, Grossman, Hillel, Shill, Holly, Soares, Holly, Lin, Honghuang, Capote, Horacio, Bergman, Howard, Chertkow, Howard, Feldman, Howard, Fillit, Howard, Rosen, Howard J, Gutman, Boris A, Koleva, Hristina, Fernandez, Hubert, Garavan, Hugh, Shim, Hyungsub, Grachev, Igor D, Richard, Irene, Filippi, Irina, Rachinsky, Irina, Wurster, Isabel, Lind, Penelope A, Hansell, Narelle K, Mintzer, Jacobo, Ziolkowski, Jaimie, Brewer, James, Lah, James J, Leverenz, James, Becker, James T, Tetrud, James, Singleton-Garvin, Jamika, Egebjerg, Jan, Cellar, Janet S, Harris, Mathew A, Pentilla, Jani, Brosch, Jared R, Tinklenberg, Jared, Karlawish, Jason H, Meyer, Javier Villanueva, Himali, Jayandra J, Poline, Jean-Baptiste, Gunter, Jeff, Kaye, Jeffrey A, Harrison, Marc B, Dalley, Jeffrey, Burns, Jeffrey M, Petrella, Jeffrey R, Mule, Jennifer, Salazar, Jennifer, Rotter, Jerome I, Yesavage, Jerome, Cedarbaum, Jesse, Jiang, Jiyang, Haswell, Courtney C, Allard, Joanne, Lord, Joanne L, Hetelle, Joel, Kwok, John B, Brockington, John, Morris, John C, Hsiao, John, Morris, John, Olichney, John, Trojanowki, John Q, Hauser, Michael, Rogers, John, Seibyl, John, Yankey, Jon, Dubow, Jordan S, Jankovic, Joseph, Quinn, Joseph, Kass, Joseph S, Taylor, Joy L, Heidebrink, Judith L, Herms, Stefan, Trollor, Julian, Fröhner, Juliane, Anderson, Karen, Blank, Karen, Crawford, Karen, Smith, Karen Ekstam, Bell, Karen L, Williams, Karen, Kieburtz, Karl, Heslenfeld, Dirk J, Gauss, Katharina, Gloer, Katherine, Johnson, Kathleen, Tingus, Kathleen, DeMarco, Kathryn, Sink, Kaycee M, Hawkins, Keith A, Johnson, Keith A, Kantarci, Kejal, Ho, New Fei, Faber, Kelley, Harless, Kelly, Makino, Kelly M, Marek, Kenneth, Spicer, Kenneth, Shianna, Kevin, Chen, Kewei, Nam, Ki Won, Martin, Kim, Poki-Walker, Kim, Hoehn, David, Seppi, Klaus, Johnson, Kris, Fargher, Kristin, Lipowski, Kristine, Espay, Kristy, Womack, Kyle, Chahine, Lama, Flashman, Laura A, Daedelow, Laura, Hoffmann, Per, Leary, Laura, Beckett, Laurel, Honig, Lawrence S, Thal, Leon, Shaw, Leslie M, Kuller, Lew, Apostolova, Liana, Teodoro, Liberty, Rees, Linda, Pizzagalli, Fabrizio, Holleran, Laurena, Lewis, Lindsay, Hergesheimer, Lindsey, Silbert, Lisa C, Ravdin, Lisa, Taylor-Reinwald, Lisa, Uribe, Liz, Schneider, Lon S, Daiello, Lori A, Richer, Louis, Poustka, Luise, Hoogman, Martine, Pirpamer, Lukas, Mesulam, M Marcel, Ismail, M Saleem, Ranola, Madelaine, Korecka, Magdalena, Raichle, Marc, Seltzer, Marc, van der Brug, Marcel, Hottenga, Jouke-Jan, Mesulam, Marek-Marsel, Carrillo, Maria, Carroll, Maria, Knol, Maria J, Kataki, Maria, Greig-Custo, Maria T, Paillere, Marie-Laure, Albert, Marilyn, Love, Marissa Natelson, Ikeda, Masashi, Mintun, Mark A, Frasier, Mark, Logue, Mark, Minton, Mark, Loeffler, Markus, Scholz, Markus, Baca, Marne, Farlow, Martin R, Sadowski, Martin, Janowitz, Deborah, Creech, Mary L, Hynes, Mary L, Quiceno, Mary, Oakley, MaryAnn, Harris, Mat, Senjem, Matt, Bernstein, Matthew, Panizzon, Matthew S, Stern, Matthew, Becerra, Mauricio, Jansen, Iris E, Witbracht, Megan, Vernooij, Meike W, Brandabur, Melanie, Keltz, Melanie, Lamar, Melissa, Yang, Mia, Ahlijanian, Michael, Borrie, Michael, Neale, Michael C, Donohue, Michael, Jia, Tianye, Lyons, Michael J, Lin, Michael, Rapp, Michael, Smolka, Michael, Weiner, Michael W, Weiner, Michael, Figurski, Michal, Perron, Michel, Assaly, Michele, Luciano, Michelle, Jockwitz, Christiane, Rainka, Michelle, Dang, Mimi, Sheikh, Mohammed O, Ghanbari, Mohsen, Gaikwad, Mrunalini, Chowdhury, Munir, Trncic, Nadira, Amin, Najaf, Johnson, Nancy, Kanai, Ryota, Kowalksi, Nancy, Monahan, Nancy, Gillespie, Nathan A, Pacini, Nathaniel, Buckholtz, Neil, Kowall, Neil, Graff-Radford, Neill R, Fox, Nick, Pavese, Nicola, Karama, Sherif, Cairns, Nigel J, Schuff, Norbert, Foster, Norm, Relkin, Norman, Oyonumo, Ntekim E, Pomara, Nunzio, James, Olga, Ogunlana, Olu, Ching, Christopher R K, Kasperaviciute, Dalia, Carmichael, Owen, Doraiswamy, P Murali, Casalin, Paola, Barone, Paolo, Fatica, Parianne, Conrod, Patricia, Johnson, Patricia Lynn, Samuels, Patricia, Aisen, Paul, Malloy, Paul, Kaufmann, Tobias, Thompson, Paul, Ogrocki, Paula, Bezivin-Frere, Pauline, Maillard, Pauline, Fontoura, Paulo, Taylor, Peggy, Hogarth, Penelope, Gowland, Penny, Davies, Peter, Kelly, Sinead, Hardy, Peter, Snyder, Peter J, Snyder, Peter, Amouyel, Philippe, Muglia, Pierandrea, Tariot, Pierre, Lu, Po H, Varma, Pradeep, Vemuri, Prashanthi, Kikuchi, Masataka, Doody, Rachelle S, Carter, Raina, Shah, Raj C, Griffith, Randall, Yeh, Randy, Duara, Ranjan, Tarawneh, Rawan, James, Raymond, Turner, Raymond Scott, Klein, Marieke, Hernando, Raymundo, Silverstein, Rebecca, Sperling, Reisa A, Wilson, Renee, Carson, Richard E, Frank, Richard, El Khouli, Riham, Koeppe, Robert A, Santulli, Robert B, Knapp, Michael, Hauser, Robert, Umek, Robert, Radtke, Rodney, Killiany, Ronald, Petersen, Ronald, Rodriguez, Rosemarie, Miranda, Ruben, Knodt, Annchen R, Bruehl, Ruediger, Xia, Rui, Swerdlow, Russell H, Ottmann, Ruth, Millenet, Sabina, Borges-Neto, Salvador, Frank, Samuel, Black, Sandra, Weintraub, Sandra, Obradov, Sanja, Krämer, Bernd, Asthana, Sanjay, Vaishnavi, Sanjeev, Dolen, Sara, Mason, Sara S, Hohmann, Sarah, Kremen, Sarah, Miller, Sarah, Walter, Sarah, Herring, Scott, Neu, Scott, Lam, Max, Aydin, Semiha, Ahmad, Shahzad, Harlan, Sherry, Sirrel, Sherye A, Lasch, Shirley, Hu, Shu-Ching, Li, Shuo, Kittur, Smita, Chowdhury, Sohini, Lancaster, Thomas M, Pawluczyk, Sonia, Maingault, Sophie, Schneider, Stacy, Seiler, Stephan, Guthrie, Stephanie, Kielb, Stephanie, Reeder, Stephanie, Correia, Stephen, Pasternak, Stephen, McMahon, Mary Agnes B, Lee, Phil H, Salloway, Stephen, Johnson, Sterling, Williams, Steve, Chao, Steven, Arnold, Steven E, Paul, Steven, Potkin, Steven, Factor, Stewart, Isaacson, Stuart, Lett, Tristram A, Kim, Sungeun, Ainscough, Susan, Schultz, Susan K, Landau, Susan, Mendick, Susan, Rountree, Susan, Ostrowizki, Suzanne, Veillette, Suzanne, van der Lee, Sven J, Desrivieres, Sylvane, Lewis, Lindsay B, Lee, T-Y, Simuni, Tanya, Foroud, Tatiana, Foroud, Tatiana M, Wong, Terence Z, Villena, Teresa, Comery, Thomas, Obisesan, Thomas O, Lopes-Cendes, Iscia, Banaschewski, Tobias, Sherer, Todd, Montine, Tom, Paus, Tomáš, Robbins, Trevor, Bromberg, Uli, Völker, Uwe, Pavlik, Valory, Arnedo, Vanessa, Kiyasova, Vera, Bates, Vernice, Logovinsky, Veronika, Sossi, Vesna, Shibley, Victoria, Frouin, Vincent, Lee, Virginia, Poewe, Werner, Jagust, William, Brooks, William M, Macciardi, Fabio, Pavlosky, William, Potter, William, Kremen, William S, Longstreth, William T, Niessen, Wiro J, Jian, Xueqiu, Stern, Yaakov, Saba, Yasaman, Cabrera, Yuliana, Grimmer, Yvonne, Marquand, Andre F, Khachaturian, Zaven, Mari, Zoltan, Mathias, Samuel R, Melzer, Tracy R, Milaneschi, Yuri, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Alzheimer’s Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN Consortium, IMAGEN Consortium, SYS Consortium, Parkinson’s Progression Markers Initiative, Stochastics, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Science and Society, Cognitive Psychology, IBBA, APH - Personalized Medicine, Complex Trait Genetics, APH - Methodology, Clinical Neuropsychology, Sociology and Social Gerontology, Amsterdam Neuroscience - Complex Trait Genetics, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA Klinische Genetica (5), Neurology, Psychiatry, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Human genetics, APH - Digital Health, Psychology, Precision Medicine Institute of Psychiatry, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Clinical Genetics, Epidemiology, Medical Informatics, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neurodegeneratives Diseases Institute (IMN-UMR CNRS 5293), Centre National de la Recherche Scientifique (CNRS), General Paediatrics, ARD - Amsterdam Reproduction and Development, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), [SDV]Life Sciences [q-bio], LOCI, Genome-wide association study, Brain mapping, 0302 clinical medicine, Cognition, Cortex (anatomy), ComputingMilieux_MISCELLANEOUS, Cerebral Cortex, 0303 health sciences, Brain Mapping, Multidisciplinary, COMMON VARIANTS, Parkinson Disease, Organ Size, Central sulcus, Magnetic Resonance Imaging, medicine.anatomical_structure, Cerebral cortex, Neuroinformatics, EXPRESSION, endocrine system, central sulcus, SURFACE-AREA, Biology, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic variation, medicine, Attention deficit hyperactivity disorder, Humans, General, Gene, METAANALYSIS, 030304 developmental biology, Progenitor, CORTICAL SULCI, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Genetic variants, Genetic Variation, Attention Deficit Disorder with Hyperactivity, Genetic Loci, Genome-Wide Association Study, functional annotation, medicine.disease, Genetic architecture, 030104 developmental biology, Evolutionary biology, OBSERVER-INDEPENDENT CHARACTERIZATION, Multiple comparisons problem, ddc:320, genome-wide association, Neuroscience, 030217 neurology & neurosurgery
Abstract

Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group., The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Published
2020

11. Age-Associated Insolubility of Parkin in Human Midbrain is Linked to Redox Balance and Sequestration of Reactive Dopamine Metabolites

Author

Tokarew, Jacqueline M., primary, El-Kodsi, Daniel N., additional, Lengacher, Nathalie A., additional, Fehr, Travis K., additional, Nguyen, Angela P., additional, Shutinoski, Bojan, additional, O’Nuallain, Brian, additional, Jin, Ming, additional, Khan, Jasmine M., additional, Ng, Andy C. H., additional, Li, Juan, additional, Jiang, Qiubo, additional, Zhang, Mei, additional, Wang, Liqun, additional, Sengupta, Rajib, additional, Barber, Kathryn R., additional, Tran, An, additional, Zandee, Stephanie, additional, Dong, Xiajun, additional, Scherzer, Clemens R., additional, Prat, Alexandre, additional, Tsai, Eve, additional, Takanashi, Masashi, additional, Hattori, Nobutaka, additional, Chan, Jennifer A., additional, Zecca, Luigi, additional, West, Andrew B., additional, Holmgren, Arne, additional, Puente, Lawrence, additional, Shaw, Gary S., additional, Toth, Gergely, additional, Woulfe, John M., additional, Taylor, Peggy, additional, Tomlinson, Julianna J., additional, and Schlossmacher, Michael G., additional

Published
2020
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12. Feasibility and safety of lumbar puncture in the Parkinson's disease research participants: Parkinson's Progression Marker Initiative (PPMI)

Author

Marek, Kenneth, Siderowf, Andrew, Seibyl, John, Coffey, Christopher, Tanner, Caroline, Tosun-Turgut, Duygu, Simuni, Tanya, Shaw, Leslie, Trojanowski, John, Singleton, Andrew, Kieburtz, Karl, Toga, Arthur, Mollenhauer, Brit, Galasko, Douglas, Poewe, Werner, Foroud, Tatiana, Poston, Kathleen, Sherer, Todd, Chowdhury, Sohini, Frasier, Mark, Kopil, Catherine, Arnedo, Vanessa, Daegele, Nichole, Casaceli, Cynthia, Dorsey, Ray, Wilson, Renee, Mahes, Sugi, Salerno, Christina, Caspell-Garcia, Chelsea, Crawford, Karen, Casalin, Paola, Malferrari, Giulia, Weisz, Mali Gani, Orr-Urtreger, Avi, Montine, Thomas, Russell, David, Dahodwala, Nabila, Giladi, Nir, Factor, Stewart, Hogarth, Penelope, Standaert, David, Hauser, Robert, Jankovic, Joseph, Saint-Hilaire, Marie, Richard, Irene, Shprecher, David, Fernandez, Hubert, Brockmann, Katrina, Rosenthal, Liana, Barone, Paolo, Espay, Alberto, Rowe, Dominic, Marder, Karen, Santiago, Anthony, Bressman, Susan, Hu, Shu-Ching, Isaacson, Stuart, Corvol, Jean-Christophe, Martinez, Javiar Ruiz, Tolosa, Eduardo, Tai, Yen, Politis, Marios, Smejdir, Debra, Rees, Linda, Williams, Karen, Kausar, Farah, Richardson, Whitney, Willeke, Diana, Peacock, Shawnees, Heim, Beatrice, Mirelman, Anat, Sommerfeld, Barbara, Freed, Alison, Wakeman, Katrina, Blair, Courtney, Guthrie, Stephanie, Harrell, Leigh, Hunter, Christine, Thomas, Cathi-Ann, James, Raymond, Zimmerman, Grace, Brown, Victoria, Mule, Jennifer, Hilt, Ella, Ribb, Kori, Ainscough, Susan, Wethington, Misty, Ranola, Madelaine, Santana, Helen Mejia, Moreno, Juliana, Raymond, Deborah, Speketer, Krista, Carvajal, Lisbeth, Carvalho, Stephanie, Croitoru, Ioana, Garrido, Alicia, Payne, Laura Marie, Viswanth, Veena, Severt, Lawrence, Facheris, Maurizio, Soares, Holly, Mintun, Mark A., Cedarbaum, Jesse, Taylor, Peggy, Biglan, Kevin, Vandenbroucke, Emily, Sheikh, Zulfiqar Haider, Bingol, Baris, Fischer, Tanya, Sardi, Pablo, Forrat, Remi, Reith, Alastair, Egebjerg, Jan, Hillert, Gabrielle Ahlberg, Saba, Barbara, Min, Chris, Umek, Robert, Mather, Joe, De Santi, Susan, Post, Anke, Boess, Frank, Taylor, Kirsten, Grachev, Igor, Avbersek, Andreja, Muglia, Pierandrea, Merchant, Kaplana, Tauscher, Johannes, Prakash, Neha, Tanner, Caroline M., Merchant, Kalpana, Chahine, Lana M., Weintraub, Daniel, Casaceli, Cindy, Herzog, Margaret, Marek, Ken, Frank, Samuel, and Jennings, Danna

Published
2019
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13. Oxidative Modifications of Parkin Underlie its Selective Neuroprotection in Adult Human Brain

Author

Tokarew, Jacqueline M., primary, El-Kodsi, Daniel N., additional, Lengacher, Nathalie A., additional, Fehr, Travis K., additional, Nguyen, Angela P., additional, O’Nuallain, Brian, additional, Jin, Ming, additional, Khan, Jasmine M., additional, Ng, Andy C. H., additional, Li, Juan, additional, Jiang, Qiubo, additional, Zhang, Mei, additional, Wang, Liqun, additional, Sengupta, Rajib, additional, Barber, Kathryn R., additional, Tran, An, additional, Zandee, Stephanie, additional, Dong, Xiajun, additional, Scherzer, Clemens R., additional, Prat, Alexandre, additional, Tsai, Eve, additional, Takanashi, Masashi, additional, Hattori, Nobutaka, additional, Chan, Jennifer A., additional, West, Andrew B., additional, Holmgren, Arne, additional, Puente, Lawrence, additional, Shaw, Gary S., additional, Toth, Gergely, additional, Woulfe, John M., additional, Taylor, Peggy, additional, Tomlinson, Julianna J., additional, and Schlossmacher, Michael G., additional

Published
2020
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14. Clinical and dopamine transporter imaging characteristics of non-manifest LRRK2 and GBA mutation carriers in the Parkinson's Progression Markers Initiative (PPMI): a cross-sectional study

Author

Simuni, Tanya, primary, Uribe, Liz, additional, Cho, Hyunkeun Ryan, additional, Caspell-Garcia, Chelsea, additional, Coffey, Christopher S, additional, Siderowf, Andrew, additional, Trojanowski, John Q, additional, Shaw, Leslie M, additional, Seibyl, John, additional, Singleton, Andrew, additional, Toga, Arthur W, additional, Galasko, Doug, additional, Foroud, Tatiana, additional, Tosun, Duygu, additional, Poston, Kathleen, additional, Weintraub, Daniel, additional, Mollenhauer, Brit, additional, Tanner, Caroline M, additional, Kieburtz, Karl, additional, Chahine, Lana M, additional, Reimer, Alyssa, additional, Hutten, Samantha J, additional, Bressman, Susan, additional, Marek, Kenneth, additional, Arnedo, Vanessa, additional, Clark, Adrienne, additional, Fraiser, Mark, additional, Kopil, Catherine, additional, Chowdhury, Sohini, additional, Sherer, Todd, additional, Daegele, Nichole, additional, Casaceli, Cynthia, additional, Dorsey, Ray, additional, Wilson, Renee, additional, Mahes, Sugi, additional, Salerno, Christina, additional, Crawford, Karen, additional, Casalin, Paola, additional, Malferrari, Giulia, additional, Weisz, Mali Gani, additional, Orr-Urtreger, Avi, additional, Montine, Thomas, additional, Baglieri, Chris, additional, Christini, Amanda, additional, Russell, David, additional, Dahodwala, Nabila, additional, Giladi, Nir, additional, Factor, Stewart, additional, Hogarth, Penelope, additional, Standaert, David, additional, Hauser, Robert, additional, Jankovic, Joseph, additional, Saint-Hilaire, Marie, additional, Richard, Irene, additional, Shprecher, David, additional, Fernandez, Hubert, additional, Brockmann, Katrina, additional, Rosenthal, Liana, additional, Barone, Paolo, additional, Espay, Alberto, additional, Rowe, Dominic, additional, Marder, Karen, additional, Santiago, Anthony, additional, Hu, Shu-Ching, additional, Isaacson, Stuart, additional, Corvol, Jean-Christophe, additional, Ruiz Martinez, Javiar, additional, Tolosa, Eduardo, additional, Tai, Yen, additional, Politis, Marios, additional, Smejdir, Debra, additional, Rees, Linda, additional, Williams, Karen, additional, Kausar, Farah, additional, Richardson, Whitney, additional, Willeke, Diana, additional, Peacock, Shawnees, additional, Sommerfeld, Barbara, additional, Freed, Alison, additional, Wakeman, Katrina, additional, Blair, Courtney, additional, Guthrie, Stephanie, additional, Harrell, Leigh, additional, Hunter, Christine, additional, Thomas, Cathi-Ann, additional, James, Raymond, additional, Zimmerman, Grace, additional, Brown, Victoria, additional, Mule, Jennifer, additional, Hilt, Ella, additional, Ribb, Kori, additional, Ainscough, Susan, additional, Wethington, Misty, additional, Ranola, Madelaine, additional, Mejia Santana, Helen, additional, Moreno, Juliana, additional, Raymond, Deborah, additional, Speketer, Krista, additional, Carvajal, Lisbeth, additional, Carvalo, Stephanie, additional, Croitoru, Ioana, additional, Garrido, Alicia, additional, Payne, Laura Marie, additional, Viswanth, Veena, additional, Severt, Lawrence, additional, Facheris, Maurizio, additional, Soares, Holly, additional, Mintun, Mark A., additional, Cedarbaum, Jesse, additional, Taylor, Peggy, additional, Biglan, Kevin, additional, Vandenbroucke, Emily, additional, Haider Sheikh, Zulfiqar, additional, Bingol, Baris, additional, Fischer, Tanya, additional, Sardi, Pablo, additional, Forrat, Remi, additional, Reith, Alastair, additional, Egebjerg, Jan, additional, Ahlberg Hillert, Gabrielle, additional, Saba, Barbara, additional, Min, Chris, additional, Umek, Robert, additional, Mather, Joe, additional, De Santi, Susan, additional, Post, Anke, additional, Boess, Frank, additional, Taylor, Kirsten, additional, Grachev, Igor, additional, Avbersek, Andreja, additional, Muglia, Pierandrea, additional, Merchant, Kaplana, additional, and Tauscher, Johannes, additional

Published
2020
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15. A user's guide for α‐synuclein biomarker studies in biological fluids: Perianalytical considerations

Author

Mollenhauer, Brit, Batrla, Richard, El‐Agnaf, Omar, Galasko, Douglas R., Lashuel, Hilal A., Merchant, Kalpana M., Shaw, Lesley M., Selkoe, Dennis J., Umek, Robert, Vanderstichele, Hugo, Zetterberg, Henrik, Zhang, Jing, Caspell‐Garcia, Chelsea, Coffey, Chris, Hutten, Samantha J., Frasier, Mark, and Taylor, Peggy

Subjects
α‐synuclein, Parkinson's disease, diagnostics, alpha-Synuclein, Reviews, Humans, Parkinson Disease, Review, Biomarker, cerebrospinal fluid, Biomarkers, standard operating procedures
Abstract

Parkinson's disease biomarkers are needed to increase diagnostic accuracy, to objectively monitor disease progression and to assess therapeutic efficacy as well as target engagement when evaluating novel drug and therapeutic strategies. This article summarizes perianalytical considerations for biomarker studies (based on immunoassays) in Parkinson's disease, with emphasis on quantifying total α‐synuclein protein in biological fluids. Current knowledge and pitfalls are discussed, and selected perianalytical variables are presented systematically, including different temperature of sample collection and types of collection tubes, gradient sampling, the addition of detergent, aliquot volume, the freezing time, and the different thawing methods. We also discuss analytical confounders. We identify gaps in the knowledge and delineate specific areas that require further investigation, such as the need to identify posttranslational modifications of α‐synuclein and antibody‐independent reference methods for quantification, as well as the analysis of potential confounders, such as comorbidities, medication, and phenotypes of Parkinson's disease in larger cohorts. This review could be used as a guideline for future Parkinson's disease biomarker studies and will require regular updating as more information arises in this growing field, including new technical developments as they become available. In addition to reviewing best practices, we also identify the current technical limitations and gaps in the knowledge that should be addressed to enable accurate and quantitative assessment of α‐synuclein levels in the clinical setting. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Published
2017

16. Feasibility and safety of lumbar puncture in the Parkinson's disease research participants: Parkinson's Progression Marker Initiative (PPMI)

Author

Prakash, Neha, primary, Caspell-Garcia, Chelsea, additional, Coffey, Christopher, additional, Siderowf, Andrew, additional, Tanner, Caroline M., additional, Kieburtz, Karl, additional, Mollenhauer, Brit, additional, Galasko, Douglas, additional, Merchant, Kalpana, additional, Foroud, Tatiana, additional, Chahine, Lana M., additional, Weintraub, Daniel, additional, Casaceli, Cindy, additional, Dorsey, Ray, additional, Wilson, Renee, additional, Herzog, Margaret, additional, Daegele, Nichole, additional, Arnedo, Vanessa, additional, Frasier, Mark, additional, Sherer, Todd, additional, Marek, Ken, additional, Frank, Samuel, additional, Jennings, Danna, additional, Simuni, Tanya, additional, Marek, Kenneth, additional, Seibyl, John, additional, Tanner, Caroline, additional, Tosun-Turgut, Duygu, additional, Shaw, Leslie, additional, Trojanowski, John, additional, Singleton, Andrew, additional, Toga, Arthur, additional, Poewe, Werner, additional, Poston, Kathleen, additional, Chowdhury, Sohini, additional, Kopil, Catherine, additional, Casaceli, Cynthia, additional, Mahes, Sugi, additional, Salerno, Christina, additional, Crawford, Karen, additional, Casalin, Paola, additional, Malferrari, Giulia, additional, Weisz, Mali Gani, additional, Orr-Urtreger, Avi, additional, Montine, Thomas, additional, Russell, David, additional, Dahodwala, Nabila, additional, Giladi, Nir, additional, Factor, Stewart, additional, Hogarth, Penelope, additional, Standaert, David, additional, Hauser, Robert, additional, Jankovic, Joseph, additional, Saint-Hilaire, Marie, additional, Richard, Irene, additional, Shprecher, David, additional, Fernandez, Hubert, additional, Brockmann, Katrina, additional, Rosenthal, Liana, additional, Barone, Paolo, additional, Espay, Alberto, additional, Rowe, Dominic, additional, Marder, Karen, additional, Santiago, Anthony, additional, Bressman, Susan, additional, Hu, Shu-Ching, additional, Isaacson, Stuart, additional, Corvol, Jean-Christophe, additional, Martinez, Javiar Ruiz, additional, Tolosa, Eduardo, additional, Tai, Yen, additional, Politis, Marios, additional, Smejdir, Debra, additional, Rees, Linda, additional, Williams, Karen, additional, Kausar, Farah, additional, Richardson, Whitney, additional, Willeke, Diana, additional, Peacock, Shawnees, additional, Heim, Beatrice, additional, Mirelman, Anat, additional, Sommerfeld, Barbara, additional, Freed, Alison, additional, Wakeman, Katrina, additional, Blair, Courtney, additional, Guthrie, Stephanie, additional, Harrell, Leigh, additional, Hunter, Christine, additional, Thomas, Cathi-Ann, additional, James, Raymond, additional, Zimmerman, Grace, additional, Brown, Victoria, additional, Mule, Jennifer, additional, Hilt, Ella, additional, Ribb, Kori, additional, Ainscough, Susan, additional, Wethington, Misty, additional, Ranola, Madelaine, additional, Santana, Helen Mejia, additional, Moreno, Juliana, additional, Raymond, Deborah, additional, Speketer, Krista, additional, Carvajal, Lisbeth, additional, Carvalho, Stephanie, additional, Croitoru, Ioana, additional, Garrido, Alicia, additional, Payne, Laura Marie, additional, Viswanth, Veena, additional, Severt, Lawrence, additional, Facheris, Maurizio, additional, Soares, Holly, additional, Mintun, Mark A., additional, Cedarbaum, Jesse, additional, Taylor, Peggy, additional, Biglan, Kevin, additional, Vandenbroucke, Emily, additional, Sheikh, Zulfiqar Haider, additional, Bingol, Baris, additional, Fischer, Tanya, additional, Sardi, Pablo, additional, Forrat, Remi, additional, Reith, Alastair, additional, Egebjerg, Jan, additional, Hillert, Gabrielle Ahlberg, additional, Saba, Barbara, additional, Min, Chris, additional, Umek, Robert, additional, Mather, Joe, additional, De Santi, Susan, additional, Post, Anke, additional, Boess, Frank, additional, Taylor, Kirsten, additional, Grachev, Igor, additional, Avbersek, Andreja, additional, Muglia, Pierandrea, additional, Merchant, Kaplana, additional, and Tauscher, Johannes, additional

Published
2019
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17. Antibody‐based methods for the measurement of α‐synuclein concentration in human cerebrospinal fluid – method comparison and round robin study

Author

Mollenhauer, Brit, primary, Bowman, Frederick DuBois, additional, Drake, Daniel, additional, Duong, Jimmy, additional, Blennow, Kaj, additional, El‐Agnaf, Omar, additional, Shaw, Leslie M., additional, Masucci, Jennifer, additional, Taylor, Peggy, additional, Umek, Robert M., additional, Dunty, Jill M., additional, Smith, Chris L., additional, Stoops, Erik, additional, Vanderstichele, Hugo, additional, Schmid, Adrian W., additional, Moniatte, Marc, additional, Zhang, Jing, additional, Kruse, Niels, additional, Lashuel, Hilal A., additional, Teunissen, Charlotte, additional, Schubert, Tanja, additional, Dave, Kuldip D., additional, Hutten, Samantha J., additional, and Zetterberg, Henrik, additional

Published
2018
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19. Additional file 6: of Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson’s disease

Author

Eidson, Lori, Kannarkat, George, Barnum, Christopher, Jianjun Chang, Jaegwon Chung, Caspell-Garcia, Chelsea, Taylor, Peggy, Mollenhauer, Brit, Schlossmacher, Michael, Ereshefsky, Larry, Yen, Mark, Kopil, Catherine, Frasier, Mark, Marek, Kenneth, Hertzberg, Vicki, and Malú Tansey

Abstract

Serum and CSF CRP levels are positively correlated in HC and PD at baseline. The relationship between serum and CSF inflammatory factors was analyzed using samples from the first collection period (baseline; time 0). There was no significant correlation between serum and CSF levels of any factor except CRP (a). Serum and CSF CRP significantly correlate in HC (slope = 325 ± 86.9, F (1, 4) = 14.0; p = 0.02) and in PD (slope = 415.5 ± 26.6, F (1, 10) = 243.8; p

Published
2017
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20. Additional file 1: of Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson’s disease

Author

Eidson, Lori, Kannarkat, George, Barnum, Christopher, Jianjun Chang, Jaegwon Chung, Caspell-Garcia, Chelsea, Taylor, Peggy, Mollenhauer, Brit, Schlossmacher, Michael, Ereshefsky, Larry, Yen, Mark, Kopil, Catherine, Frasier, Mark, Marek, Kenneth, Hertzberg, Vicki, and Malú Tansey

Abstract

Regression analysis of each analyte by individual and means and SEM by analyte across time. (PDF 1526 kb)

Published
2017
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21. Additional file 2: of Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson’s disease

Author

Eidson, Lori, Kannarkat, George, Barnum, Christopher, Jianjun Chang, Jaegwon Chung, Caspell-Garcia, Chelsea, Taylor, Peggy, Mollenhauer, Brit, Schlossmacher, Michael, Ereshefsky, Larry, Yen, Mark, Kopil, Catherine, Frasier, Mark, Marek, Kenneth, Hertzberg, Vicki, and Malú Tansey

Subjects
body regions, nervous system, fungi
Abstract

Serum TNF and NGAL are significantly different between PD and HC at time 0. (PDF 561 kb)

Published
2017
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22. Additional file 4: of Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson’s disease

Author

Eidson, Lori, Kannarkat, George, Barnum, Christopher, Jianjun Chang, Jaegwon Chung, Caspell-Garcia, Chelsea, Taylor, Peggy, Mollenhauer, Brit, Schlossmacher, Michael, Ereshefsky, Larry, Yen, Mark, Kopil, Catherine, Frasier, Mark, Marek, Kenneth, Hertzberg, Vicki, and Malú Tansey

Subjects
body regions, nervous system, fungi
Abstract

PD and HC subjects have different relationships between serum and CSF inflammation. (PDF 801 kb)

Published
2017
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23. Additional file 5: of Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson’s disease

Author

Eidson, Lori, Kannarkat, George, Barnum, Christopher, Jianjun Chang, Jaegwon Chung, Caspell-Garcia, Chelsea, Taylor, Peggy, Mollenhauer, Brit, Schlossmacher, Michael, Ereshefsky, Larry, Yen, Mark, Kopil, Catherine, Frasier, Mark, Marek, Kenneth, Hertzberg, Vicki, and Malú Tansey

Abstract

Summary of relationships between inflammation and Aβs and α-synuclein in PD and HC. (PDF 2346 kb)

Published
2017
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24. Additional file 8: of Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson’s disease

Author

Eidson, Lori, Kannarkat, George, Barnum, Christopher, Jianjun Chang, Jaegwon Chung, Caspell-Garcia, Chelsea, Taylor, Peggy, Mollenhauer, Brit, Schlossmacher, Michael, Ereshefsky, Larry, Yen, Mark, Kopil, Catherine, Frasier, Mark, Marek, Kenneth, Hertzberg, Vicki, and Malú Tansey

Subjects
body regions, nervous system, mental disorders, fungi
Abstract

CSF IFNγ and serum IL-8 positively correlated with UPDRS components at baseline in PD subjects. (PDF 563 kb)

Published
2017
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26. Additional file 3: of Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson’s disease

Author

Eidson, Lori, Kannarkat, George, Barnum, Christopher, Jianjun Chang, Jaegwon Chung, Caspell-Garcia, Chelsea, Taylor, Peggy, Mollenhauer, Brit, Schlossmacher, Michael, Ereshefsky, Larry, Yen, Mark, Kopil, Catherine, Frasier, Mark, Marek, Kenneth, Hertzberg, Vicki, and Malú Tansey

Subjects
body regions, nervous system, fungi
Abstract

Serum TNF, IFNγ, and NGAL are different between PD and HC irrespective of time. (PDF 1693 kb)

Published
2017
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27. Additional file 9: of Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson’s disease

Author

Eidson, Lori, Kannarkat, George, Barnum, Christopher, Jianjun Chang, Jaegwon Chung, Caspell-Garcia, Chelsea, Taylor, Peggy, Mollenhauer, Brit, Schlossmacher, Michael, Ereshefsky, Larry, Yen, Mark, Kopil, Catherine, Frasier, Mark, Marek, Kenneth, Hertzberg, Vicki, and Malú Tansey

Subjects
3. Good health
Abstract

Linear discriminant analysis reveals sensitivity and selectivity of analytes in discriminating between HC and PD. Serum and CSF levels of IL-6 (a), serum IL-6 (b). Serum and CSF IL-8, TNF, NGAL, and IFNγ, and CSF α-synuclein, Aβ40 and Aβ42 (d), serum IL-8, TNF, NGAL, IFNγ, and CSF α-synuclein, Aβ40, and Aβ42 (e), serum and CSF IL-8, TNF, NGAL, IFNγ, and CSF Aβ40 (f), serum and CSF IL-8, TNF, NGAL, IFNγ, and CSF Aβ42 (g), serum and CSF IL-8, TNF, NGAL, IFNγ, and CSF α-synuclein (h), serum and CSF IL-8, TNF, NGAL, IFNγ (i), serum IL-8, TNF, NGAL, IFNγ, and CSF Aβ42 (j), serum IL-8, TNF, NGAL, IFNγ, and CSF α-synuclein (k), serum IL-8, TNF, NGAL, IFNγ, and CSF Aβ40 (l), serum and CSF TNF, NGAL, IFNγ, and CSF α-synuclein, Aβ40, and Aβ42 (m), serum TNF, NGAL, IFNγ, and CSF α-synuclein, and Aβ42 (n), serum TNF, NGAL, and IFNγ (o), serum and CSF TNF, NGAL, and IFNγ (p), serum TNF, NGAL, and IFNγ and CSF α-synuclein, Aβ40, and Aβ42 (q), serum TNF and CSF α-synuclein, and Aβ42 (r), serum TNF and CSF Aβ42 (s), serum IL-8, TNF, NGAL, and IFNγ (t). The x axis is the percentage of correct categorization into a group, and the red line is set at the lowest percentage of correct categorizations for the factor or factors considered. The y axis is the collection hour. (PDF 239 kb)

Published
2017
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28. O2‐09‐04: HARMONIZATION OF IMMUNOCHEMICAL METHODS FOR MEASUREMENT OF α‐SYNUCLEIN IN HUMAN CEREBROSPINAL FLUID: A ROUND ROBIN STUDY APPROACH

Author

Hutten, Samantha J., primary, Mollenhauer, Brit, additional, Bowman, F Dubois, additional, Drake, Daniel, additional, Duong, Jimmy, additional, Blennow, Kaj, additional, Corradini, Veronika, additional, El-Agnaf, Omar M.A., additional, Shaw, Leslie M., additional, Masucci, Jennifer, additional, Taylor, Peggy, additional, Umek, Robert M., additional, Dunty, Jill, additional, Smith, Chris L., additional, Stoops, Erik, additional, Vanderstichele, Hugo Marcel, additional, Schmid, Adrien W., additional, Moniatte, Marc, additional, Zhang, Jing, additional, Kruse, Niels, additional, Lashuel, Hilal A., additional, Teunissen, Charlotte E., additional, Schubert, Tanja, additional, Dave, Kuldip D., additional, and Zetterberg, Henrik, additional

Published
2018
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29. Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson’s disease

Author

Eidson, Lori N., primary, Kannarkat, George T., additional, Barnum, Christopher J., additional, Chang, Jianjun, additional, Chung, Jaegwon, additional, Caspell-Garcia, Chelsea, additional, Taylor, Peggy, additional, Mollenhauer, Brit, additional, Schlossmacher, Michael G., additional, Ereshefsky, Larry, additional, Yen, Mark, additional, Kopil, Catherine, additional, Frasier, Mark, additional, Marek, Kenneth, additional, Hertzberg, Vicki S., additional, and Tansey, Malú G., additional

Published
2017
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33. Diagnosis of Parkinson's disease on the basis of clinical and genetic classification: A population-based modelling study

Author

Nalls, Mike A, McLean, Cory Y, Hardy, John, Seppi, Klaus, Reiter, Eva, Shill, Holly, Fernandez, Hubert, Ahmed, Anwar, Berg, Daniela, Wurster, Isabel, Mari, Zoltan, Brooks, David, Pavese, Nicola, Gasser, Thomas, Barone, Paolo, Isaacson, Stuart, Espay, Alberto, Rowe, Dominic, Brandabur, Melanie, Tetrud, James, Liang, Grace, Marder, Karen, Corvol, Jean-Christophe, Martí Masso, Jose Felix, Brice, Alexis, Tolosa, Eduardo, Aasly, Jan O, Giladi, Nir, Stefanis, Leonidas, Leary, Laura, Riordan, Cheryl, Rees, Linda, Sommerfeld, Barbara, Wood-Siverio, Cathy, Portillo, Alicia, Price, T Ryan, Lenahan, Art, Williams, Karen, Guthrie, Stephanie, Rawlins, Ashlee, Harlan, Sherry, Hunter, Christine, Tran, Baochan, Darin, Abigail, Linder, Carly, Todd, Gretchen, Nicolas, Aude, Thomas, Cathi-Ann, James, Raymond, Deeley, Cheryl, Bishop, Courtney, Sprenger, Fabienne, Willeke, Diana, Obradov, Sanja, Mule, Jennifer, Monahan, Nancy, Gauss, Katharina, Keller, Margaux F, Comyns, Kathleen, Fontaine, Deborah, Gigliotti, Christina, McCoy, Arita, Dunlop, Becky, Shah, Bina, Ainscough, Susan, James, Angela, Silverstein, Rebecca, Espay, Kristy, Molony, Cliona, Ranola, Madelaine, Santana, Helen M, Ngono, Nelly, Rezola, Elisabet, Rolan, Delores Vilas, Waro, Bjorg, Mirlman, Anat, Stamelou, Maria, Comery, Thomas, Papapetropoulos, Spyros, Gibbs, J Raphael, Ravina, Bernard, Grachev, Igor D, Dubow, Jordan S, Ahlijanian, Michael, Soares, Holly, Ostrowizki, Suzanne, Fontoura, Paulo, Chalker, Alison, Hewitt, David L, van der Brug, Marcel, Chen-Plotkin, Alice, Reith, Alastair D, Taylor, Peggy, Egebjerg, Jan, Minton, Mark, Siderowf, Andrew, Muglia, Pierandrea, Umek, Robert, Catafau, Ana, Suh, Eunran, Rick, Jacqueline, Letson, Christopher, Fiandaca, Massimo S, Mapstone, Mark, Federoff, Howard J, Noyce, Alastair J, Morris, Huw, Van Deerlin, Vivianna M, Weintraub, Daniel, Zabetian, Cyrus, Hernandez, Dena G, Eberly, Shirley, Lesage, Suzanne, Mullins, Meghan, Conley, Emily Drabant, Northover, Carrie A M, Frasier, Mark, Marek, Ken, Day-Williams, Aaron G, Stone, David J, Ioannidis, John P A, Singleton, Andrew B, Hutten, Samantha J, investigators, Parkinson's Disease Biomarkers Program and Parkinson's Progression Marker Initiative, Bowman, Dubois, Dawson, Ted, Dewey, Richard, German, Dwight Charles, Huang, Xuemei, Petyuk, Vladislav, Scherzer, Clemens, Vaillancourt, David, Gwinn, Katrina, West, Andrew, Zhang, Jing, Marek, Kenneth, Jennings, Danna, Lasch, Shirley, Tanner, Caroline, Simuni, Tanya, Coffey, Christopher, Kieburtz, Karl, Wilson, Renee, Sutherland, Margaret, Poewe, Werner, Mollenhauer, Brit, Galasko, Douglas, Foroud, Tatiana, Sherer, Todd, Chowdhury, Sohini, Kopil, Catherine, Arnedo, Vanessa, Casaceli, Cynthia, Martinez, Maria, Seibyl, John, Mendick, Susan, Schuff, Norbert, Caspell, Chelsea, Uribe, Liz, Foster, Eric, Gloer, Katherine, Yankey, Jon, Toga, Arthur, Crawford, Karen, Heutink, Peter, Smith, Danielle Elise, Casalin, Paola, Malferrari, Giulia, Trojanowski, John, Shaw, Les, Singleton, Andrew, Halter, Cheryl, Russell, David, Factor, Stewart, Hogarth, Penelope, Williams, Nigel M, Standaert, David, Hauser, Robert, Jankovic, Joseph, Stern, Matthew, Chahine, Lama, Hu, Shu-Ching, Frank, Samuel, Trenkwalder, Claudia, Oertel, Wolfgang, and Richard, Irene

Subjects
Male, Aging, Parkinson's disease, Genome-wide association study, Disease, Neurodegenerative, Cohort Studies, genetics [Parkinson Disease], Models, 2.1 Biological and endogenous factors, Family history, Aetiology, education.field_of_study, screening and diagnosis, Parkinson's Disease, Aged, Disease Progression, Female, Humans, Middle Aged, Parkinson Disease, Prodromal Symptoms, Models, Statistical, Neurology (clinical), Statistical, Detection, Cohort, Neurological, Biomarker (medicine), diagnosis [Parkinson Disease], Cohort study, 4.2 Evaluation of markers and technologies, medicine.medical_specialty, Population, Clinical Sciences, Parkinson's Disease Biomarkers Program and Parkinson's Progression Marker Initiative investigators, Article, Clinical Research, Internal medicine, medicine, ddc:610, education, Neurology & Neurosurgery, business.industry, Prevention, Neurosciences, medicine.disease, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Physical therapy, business
Abstract

Summary Background Accurate diagnosis and early detection of complex diseases, such as Parkinson's disease, has the potential to be of great benefit for researchers and clinical practice. We aimed to create a non-invasive, accurate classification model for the diagnosis of Parkinson's disease, which could serve as a basis for future disease prediction studies in longitudinal cohorts. Methods We developed a model for disease classification using data from the Parkinson's Progression Marker Initiative (PPMI) study for 367 patients with Parkinson's disease and phenotypically typical imaging data and 165 controls without neurological disease. Olfactory function, genetic risk, family history of Parkinson's disease, age, and gender were algorithmically selected by stepwise logistic regression as significant contributors to our classifying model. We then tested the model with data from 825 patients with Parkinson's disease and 261 controls from five independent cohorts with varying recruitment strategies and designs: the Parkinson's Disease Biomarkers Program (PDBP), the Parkinson's Associated Risk Study (PARS), 23andMe, the Longitudinal and Biomarker Study in PD (LABS-PD), and the Morris K Udall Parkinson's Disease Research Center of Excellence cohort (Penn-Udall). Additionally, we used our model to investigate patients who had imaging scans without evidence of dopaminergic deficit (SWEDD). Findings In the population from PPMI, our initial model correctly distinguished patients with Parkinson's disease from controls at an area under the curve (AUC) of 0·923 (95% CI 0·900–0·946) with high sensitivity (0·834, 95% CI 0·711–0·883) and specificity (0·903, 95% CI 0·824–0·946) at its optimum AUC threshold (0·655). All Hosmer-Lemeshow simulations suggested that when parsed into random subgroups, the subgroup data matched that of the overall cohort. External validation showed good classification of Parkinson's disease, with AUCs of 0·894 (95% CI 0·867–0·921) in the PDBP cohort, 0·998 (0·992–1·000) in PARS, 0·955 (no 95% CI available) in 23andMe, 0·929 (0·896–0·962) in LABS-PD, and 0·939 (0·891–0·986) in the Penn-Udall cohort. Four of 17 SWEDD participants who our model classified as having Parkinson's disease converted to Parkinson's disease within 1 year, whereas only one of 38 SWEDD participants who were not classified as having Parkinson's disease underwent conversion (test of proportions, p=0·003). Interpretation Our model provides a potential new approach to distinguish participants with Parkinson's disease from controls. If the model can also identify individuals with prodromal or preclinical Parkinson's disease in prospective cohorts, it could facilitate identification of biomarkers and interventions. Funding National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Michael J Fox Foundation.

Published
2015

34. Impact of Pre-Analytical Differences on Biomarkers in the ADNI and PPMI Studies: Implications in the Era of Classifying Disease Based on Biomarkers.

Author

Stewart, Tessandra, Shi, Min, Mehrotra, Aanchal, Aro, Patrick, Soltys, David, Kerr, Kathleen F., Zabetian, Cyrus P., Peskind, Elaine R., Taylor, Peggy, Shaw, Leslie M., Trojanowski, John Q., Zhang, Jing, and from the Alzheimer’s Disease Neuroimaging Initiative, and Alzheimer’s Disease Neuroimaging Initiative

Subjects
PARKINSON'S disease, ALZHEIMER'S disease, BIOMARKERS, CEREBROSPINAL fluid, NEURODEGENERATION
Abstract

Background: Neurodegenerative diseases require characterization based on underlying biology using biochemical biomarkers. Mixed pathology complicates discovery of biomarkers and characterization of cohorts, but inclusion of greater numbers of patients with different, related diseases with frequently co-occurring pathology could allow better accuracy. Combining cohorts collected from different studies would be a more efficient use of resources than recruiting subjects from each population of interest for each study.Objective: To explore the possibility of combining existing datasets by controlling pre-analytic variables in the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Parkinson's Progression Markers Initiative (PPMI) studies.Methods: Cerebrospinal fluid (CSF) was collected and processed from 30 subjects according to both the ADNI and PPMI protocols. Relationships between reported levels of Alzheimer's disease (AD) and Parkinson's disease (PD) biomarkers in the same subject under each protocol were examined.Results: Protocol-related differences were observed for Aβ, but not t-tau or α-syn, and trended different for p-tau and pS129. Values of α-syn differed by platform. Conversion of α-syn values between ADNI and PPMI platforms did not completely eliminate differences in distribution.Discussion: Factors not captured in the pre-analytical sample handling influence reported biomarker values. Assay standardization and better harmonized characterization of cohorts should be included in future studies of CSF biomarkers. [ABSTRACT FROM AUTHOR]

Published
2019
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35. Antibody‐based methods for the measurement of α‐synuclein concentration in human cerebrospinal fluid – method comparison and round robin study.

Author

Mollenhauer, Brit, Bowman, Frederick DuBois, Drake, Daniel, Duong, Jimmy, Blennow, Kaj, El‐Agnaf, Omar, Shaw, Leslie M., Masucci, Jennifer, Taylor, Peggy, Umek, Robert M., Dunty, Jill M., Smith, Chris L., Stoops, Erik, Vanderstichele, Hugo, Schmid, Adrian W., Moniatte, Marc, Zhang, Jing, Kruse, Niels, Lashuel, Hilal A., and Teunissen, Charlotte

Subjects
IMMUNOGLOBULINS, SYNUCLEINS, CEREBROSPINAL fluid, NEURODEGENERATION, IMMUNOCHEMISTRY
Abstract

α‐Synuclein is the major component of Lewy bodies and a candidate biomarker for neurodegenerative diseases in which Lewy bodies are common, including Parkinson's disease and dementia with Lewy bodies. A large body of literature suggests that these disorders are characterized by reduced concentrations of α‐synuclein in cerebrospinal fluid (CSF), with overlapping concentrations compared to healthy controls and variability across studies. Several reasons can account for this variability, including technical ones, such as inter‐assay and inter‐laboratory variation (reproducibility). We compared four immunochemical methods for the quantification of α‐synuclein concentration in 50 unique CSF samples. All methods were designed to capture most of the existing α‐synuclein forms in CSF ('total' α‐synuclein). Each of the four methods showed high analytical precision, excellent correlation between laboratories (R2 0.83–0.99), and good correlation with each other (R2 0.64–0.93), although the slopes of the regression lines were different between the four immunoassays. The use of common reference CSF samples decreased the differences in α‐synuclein concentration between detection methods and technologies. Pilot data on an immunoprecipitation mass spectrometry (IP‐MS) method is also presented. Our results suggest that the four immunochemical methods and the IP‐MS method measure similar forms of α‐synuclein and that a common reference material would allow harmonization of results between immunoassays. α‐Synuclein is a synaptic protein that forms intracellular Lewy body inclusions in Parkinson's disease and other so called synuclein aggregation disorders. There are several methods to measure α‐synuclein concentration in human cerebrospinal fluid, where it is a candidate diagnostic and prognostic biomarker. In the current paper, we compared the analytical characteristics of four immunochemical (MSD, BioLegnd, Adx, and Roche) and one mass spectrometry‐based method. Variance component analysis partitions the total variance associated with 49 sample measured by site, kit lot, and replicate. The results show that the different methods measure similar forms of α‐synuclein and that a common reference material would allow for assay harmonization, which will be important in studies evaluating drugs that target α‐synuclein pathology specifically. [ABSTRACT FROM AUTHOR]

Published
2019
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36. Monitoring of 30 marker candidates in early Parkinson disease as progression markers

Author

Mollenhauer, Brit, primary, Zimmermann, Johannes, additional, Sixel-Döring, Friederike, additional, Focke, Niels K., additional, Wicke, Tamara, additional, Ebentheuer, Jens, additional, Schaumburg, Martina, additional, Lang, Elisabeth, additional, Trautmann, Ellen, additional, Zetterberg, Henrik, additional, Taylor, Peggy, additional, Friede, Tim, additional, and Trenkwalder, Claudia, additional

Published
2016
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37. HARMONIZATION OF IMMUNOCHEMICAL METHODS FOR MEASUREMENT OF α-SYNUCLEIN IN HUMAN CEREBROSPINAL FLUID: A ROUND ROBIN STUDY APPROACH

Author

Hutten, Samantha J., Mollenhauer, Brit, Bowman, F Dubois, Drake, Daniel, Duong, Jimmy, Blennow, Kaj, Corradini, Veronika, El-Agnaf, Omar M.A., Shaw, Leslie M., Masucci, Jennifer, Taylor, Peggy, Umek, Robert M., Dunty, Jill, Smith, Chris L., Stoops, Erik, Vanderstichele, Hugo Marcel, Schmid, Adrien W., Moniatte, Marc, Zhang, Jing, Kruse, Niels, Lashuel, Hilal A., Teunissen, Charlotte E., Schubert, Tanja, Dave, Kuldip D., and Zetterberg, Henrik

Published
2018
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39. Building on Strengths.

Author

TAYLOR, PEGGY and MURPHY, CHARLIE

Abstract

An excerpt from the book "Catch the Fire: An Art-Full Guide to Unleashing the Creative Power of Youth" by Peggy Taylor and Charlie Murphy is presented.

Published
2014

41. Thank God, Daddy was a 'college nigger'.

Author

TAYLOR, PEGGY

Subjects
*LYNCHING, *TRAFFIC accidents, *WHITE women, *FUNERALS, *HIGH school reunions
Abstract

The author talks about visiting the National Memorial for Peace and Justice by referring to her father, Franklyn Watson Taylor Sr., a former college professor, and her half-brother Franklyn Watson Taylor Jr., who escaped lynching in the 1930s after a car crash that left a white woman dead. She also mentions her memories of visiting Montgomery, Alabama, for her parents' funerals, high school reunion, and the 60th anniversary of the Montgomery Chapter of the Links.

Published
2018

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