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404 results on '"Scherzer, Clemens R."'

1. Investigation of the genetic aetiology of Lewy body diseases with and without dementia

Author

Wu, Lesley Yue, Real, Raquel, Martinez-Carrasco, Alejandro, Chia, Ruth, Lawton, Michael A, Shoai, Maryam, Bresner, Catherine, Blauwendraat, Cornelis, Singleton, Andrew B, Ryten, Mina, Abramzon, Yevgeniya, Ahmed, Sarah, Alba, Camille, Albert, Marilyn S, Bacikova, Dagmar, Barrett, Matthew J, Beach, Thomas G, Bennett, David A, Besser, Lilah M, Bigio, Eileen H, Boeve, Bradley F, Bohannan, Ryan C, Caraway, Chad A, Palma, Jose-Alberto, Dalgard, Clifton L, Dickson, Dennis, Ding, Jinhui, Faber, Kelley, Ferman, Tanis, Ferrucci, Luigi, Flanagan, Margaret E, Foroud, Tatiana M, Ghetti, Bernardino, Gibbs, J Raphael, Goate, Alison, Goldstein, David, Graff-Radford, Neill R, Hu, Heng-Chen, Hupalo, Daniel, Kaiser, Scott M, Kaufmann, Horacio, Kim, Ronald C, Klein, Gregory, Kukull, Walter, Kuzma, Amanda, Leverenz, James, Lopez, Grisel, Mao, Qinwen, Martinez-McGrath, Elisa, Masliah, Eliezer, Monuki, Ed, Newell, Kathy L, Norcliffe-Kaufmann, Lucy, Perkins, Matthew, Pletnikova, Olga, Renton, Alan E, Resnick, Susan M, Ross, Owen A, Sabir, Marya S, Scherzer, Clemens R, Scholz, Sonja W, Serrano, Geidy, Shakkotai, Vikram, Sidransky, Ellen, Tanaka, Toshiko, Tayebi, Nahid, Traynor, Bryan J, Troncoso, Juan C, Viollet, Coralie, Walton, Ronald L, Woltjer, Randy, Wszolek, Zbigniew K, Black, Sandra E, Gan-Or, Ziv, Keith, Julia, Masellis, Mario, Rogaeva, Ekaterina, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Ferrari, Raffaele, Gentleman, Steve, Hardy, John A, Hodges, Angela K, Love, Seth, McKeith, Ian, Morris, Christopher M, Morris, Huw R, Palmer, Laura, Pickering-Brown, Stuart, Reynolds, Regina H, Thomas, Alan J, Tilley, Bension S, Troakes, Claire, Brett, Francesca, Brice, Alexis, and Duyckaerts, Charles

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Human Genome, Genetics, Brain Disorders, Lewy Body Dementia, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Parkinson's Disease, Neurodegenerative, Dementia, Aging, Prevention, Acquired Cognitive Impairment, Clinical Research, 2.1 Biological and endogenous factors, Neurological, International Lewy Body Dementia Genomics Consortium, APOE, Lewy body diseases, dementia, genome-wide association studies, Clinical sciences, Biological psychology
Abstract

Up to 80% of Parkinson's disease patients develop dementia, but time to dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents with clinical features similar to Parkinson's disease dementia, but cognitive impairment precedes or coincides with motor onset. It remains controversial whether dementia with Lewy bodies and Parkinson's disease dementia are distinct conditions or represent part of a disease spectrum. The biological mechanisms underlying disease heterogeneity, in particular the development of dementia, remain poorly understood, but will likely be the key to understanding disease pathways and, ultimately, therapy development. Previous genome-wide association studies in Parkinson's disease and dementia with Lewy bodies/Parkinson's disease dementia have identified risk loci differentiating patients from controls. We collated data for 7804 patients of European ancestry from Tracking Parkinson's, The Oxford Discovery Cohort, and Accelerating Medicine Partnership-Parkinson's Disease Initiative. We conducted a discrete phenotype genome-wide association study comparing Lewy body diseases with and without dementia to decode disease heterogeneity by investigating the genetic drivers of dementia in Lewy body diseases. We found that risk allele rs429358 tagging APOEe4 increases the odds of developing dementia, and that rs7668531 near the MMRN1 and SNCA-AS1 genes and an intronic variant rs17442721 tagging LRRK2 G2019S on chromosome 12 are protective against dementia. These results should be validated in autopsy-confirmed cases in future studies.

Published
2024

3. Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping

Author

Ndayisaba, Alain, Pitaro, Ariana T., Willett, Andrew S., Jones, Kristie A., de Gusmao, Claudio Melo, Olsen, Abby L., Kim, Jisoo, Rissanen, Eero, Woods, Jared K., Srinivasan, Sharan R., Nagy, Anna, Nagy, Amanda, Mesidor, Merlyne, Cicero, Steven, Patel, Viharkumar, Oakley, Derek H., Tuncali, Idil, Taglieri-Noble, Katherine, Clark, Emily C., Paulson, Jordan, Krolewski, Richard C., Ho, Gary P., Hung, Albert Y., Wills, Anne-Marie, Hayes, Michael T., Macmore, Jason P., Warren, Luigi, Bower, Pamela G., Langer, Carol B., Kellerman, Lawrence R., Humphreys, Christopher W., Glanz, Bonnie I., Dielubanza, Elodi J., Frosch, Matthew P., Freeman, Roy L., Gibbons, Christopher H., Stefanova, Nadia, Chitnis, Tanuja, Weiner, Howard L., Scherzer, Clemens R., Scholz, Sonja W., Vuzman, Dana, Cox, Laura M., Wenning, Gregor, Schmahmann, Jeremy D., Gupta, Anoopum S., Novak, Peter, Young, Geoffrey S., Feany, Mel B., Singhal, Tarun, and Khurana, Vikram

Published
2024
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4. Genetic evaluation of dementia with Lewy bodies implicates distinct disease subgroups.

Author

Kaivola, Karri, Shah, Zalak, Chia, Ruth, Black, Sandra E, Gan-Or, Ziv, Keith, Julia, Masellis, Mario, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Calvo, Andrea, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Reijko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hardy, John A, Hodges, Angela K, Love, Seth, McKeith, Ian G, Morris, Christopher M, Morris, Huw R, Palmer, Laura, Pickering-Brown, Stuart, Ryten, Mina, Thomas, Alan J, Troakes, Claire, Albert, Marilyn S, Barrett, Matthew J, Beach, Thomas G, Bekris, Lynn M, Bennett, David A, Boeve, Bradley F, Dalgard, Clifton L, Dawson, Ted M, Dickson, Dennis W, Faber, Kelley, Ferman, Tanis, Ferrucci, Luigi, Flanagan, Margaret E, Foroud, Tatiana M, Ghetti, Bernardino, Gibbs, J Raphael, Goate, Alison, Goldstein, David S, Graff-Radford, Neill R, Kaufmann, Horacio, Kukull, Walter A, Leverenz, James B, Mao, Qinwen, Masliah, Eliezer, Monuki, Edwin, Newell, Kathy L, Palma, Jose Alberto, Pletnikova, Olga, Renton, Alan E, Resnick, Susan M, Rosenthal, Liana S, Ross, Owen A, Scherzer, Clemens R, Serrano, Geidy E, Shakkottai, Vikram G, Sidransky, Ellen, Tanaka, Toshiko, Topol, Eric, Torkamani, Ali, Troncoso, Juan C, Woltjer, Randy, Wszolek, Zbigniew K, and Scholz, Sonja W

Subjects
Genetics, Lewy Body Dementia, Neurodegenerative, Aging, Brain Disorders, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Alzheimer's Disease, Acquired Cognitive Impairment, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Alzheimer Disease, Apolipoprotein E4, Genome-Wide Association Study, Humans, Lewy Body Disease, alpha-Synuclein, International LBD Genomics Consortium, APOE, Alzheimer’s disease, co-pathology, dementia with Lewy bodies, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

The APOE locus is strongly associated with risk for developing Alzheimer's disease and dementia with Lewy bodies. In particular, the role of the APOE ε4 allele as a putative driver of α-synuclein pathology is a topic of intense debate. Here, we performed a comprehensive evaluation in 2466 dementia with Lewy bodies cases versus 2928 neurologically healthy, aged controls. Using an APOE-stratified genome-wide association study approach, we found that GBA is associated with risk for dementia with Lewy bodies in patients without APOE ε4 (P = 6.58 × 10-9, OR = 3.41, 95% CI = 2.25-5.17), but not with dementia with Lewy bodies with APOE ε4 (P = 0.034, OR = 1.87, 95%, 95% CI = 1.05-3.37). We then divided 495 neuropathologically examined dementia with Lewy bodies cases into three groups based on the extent of concomitant Alzheimer's disease co-pathology: pure dementia with Lewy bodies (n = 88), dementia with Lewy bodies with intermediate Alzheimer's disease co-pathology (n = 66) and dementia with Lewy bodies with high Alzheimer's disease co-pathology (n = 341). In each group, we tested the association of the APOE ε4 against the 2928 neurologically healthy controls. Our examination found that APOE ε4 was associated with dementia with Lewy bodies + Alzheimer's disease (P = 1.29 × 10-32, OR = 4.25, 95% CI = 3.35-5.39) and dementia with Lewy bodies + intermediate Alzheimer's disease (P = 0.0011, OR = 2.31, 95% CI = 1.40-3.83), but not with pure dementia with Lewy bodies (P = 0.31, OR = 0.75, 95% CI = 0.43-1.30). In conclusion, although deep clinical data were not available for these samples, our findings do not support the notion that APOE ε4 is an independent driver of α-synuclein pathology in pure dementia with Lewy bodies, but rather implicate GBA as the main risk gene for the pure dementia with Lewy bodies subgroup.

Published
2022

5. Correction to: Clinical trial-ready patient cohorts for multiple system atrophy: coupling biospecimen and iPSC banking to longitudinal deep-phenotyping

Author

Ndayisaba, Alain, Pitaro, Ariana T., Willett, Andrew S., Jones, Kristie A., de Gusmao, Claudio Melo, Olsen, Abby L., Kim, Jisoo, Rissanen, Eero, Woods, Jared K., Srinivasan, Sharan R., Nagy, Anna, Nagy, Amanda, Mesidor, Merlyne, Cicero, Steven, Patel, Viharkumar, Oakley, Derek H., Tuncali, Idil, Taglieri-Noble, Katherine, Clark, Emily C., Paulson, Jordan, Krolewski, Richard C., Ho, Gary P., Hung, Albert Y., Wills, Anne-Marie, Hayes, Michael T., Macmore, Jason P., Warren, Luigi, Bower, Pamela G., Langer, Carol B., Kellerman, Lawrence R., Humphreys, Christopher W., Glanz, Bonnie I., Dielubanza, Elodi J., Frosch, Matthew P., Freeman, Roy L., Gibbons, Christopher H., Stefanova, Nadia, Chitnis, Tanuja, Weiner, Howard L., Scherzer, Clemens R., Scholz, Sonja W., Vuzman, Dana, Cox, Laura M., Wenning, Gregor, Schmahmann, Jeremy D., Gupta, Anoopum S., Novak, Peter, Young, Geoffrey S., Feany, Mel B., Singhal, Tarun, and Khurana, Vikram

Published
2024
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6. Differential blood DNA methylation across Lewy body dementias

Author

Nasamran, Chanond A, Sachan, Anubhav Nikunj Singh, Mott, Jennifer, Kuras, Yuliya I, Scherzer, Clemens R, Study, Harvard Biomarkers, Ricciardelli, Eugenia, Jepsen, Kristen, Edland, Steven D, Fisch, Kathleen M, and Desplats, Paula

Subjects
Biomedical and Clinical Sciences, Neurosciences, Aging, Acquired Cognitive Impairment, Genetics, Parkinson's Disease, Brain Disorders, Lewy Body Dementia, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Research, Dementia, Alzheimer's Disease Related Dementias (ADRD), 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, biomarker, blood, cognitive scores, dementia, dementia with Lewy bodies, DNA methylation, epigenetics, Lewy body diseases, Parkinson&apos, s disease dementia, REM sleep behavior disorder, Parkinson's disease dementia, Biological psychology
Abstract

IntroductionDementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by cognitive alterations, visual hallucinations, and motor impairment. Diagnosis is based on type and timing of clinical manifestations; however, determination of clinical subtypes is challenging. The utility of blood DNA methylation as a biomarker for Lewy body disorders (LBD) is mostly unexplored.MethodsWe performed a cross-sectional analysis of blood methylation in 42 DLB and 50 PDD cases applying linear models to compare groups and logistic least absolute shrinkage and selection operator regression to explore the discriminant power of methylation signals.ResultsDLB blood shows differential methylation compared to PDD. Some methylation changes associate with core features of LBD. Sets of probes show high predictive value to discriminate between variants.DiscussionOur study is the first to explore LBD blood methylation. Despite overlapping clinical presentation, we detected differential epigenetic signatures that, if confirmed in independent cohorts, could be developed into useful biomarkers.

Published
2021

9. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias

Author

Soltis, Anthony R., Viollet, Coralie, Sukumar, Gauthaman, Alba, Camille, Lott, Nathaniel, McGrath Martinez, Elisa, Tuck, Meila, Singh, Jatinder, Bacikova, Dagmar, Zhang, Xijun, Hupalo, Daniel N., Adeleye, Adelani, Wilkerson, Matthew D., Pollard, Harvey B., Dalgard, Clifton L., Black, Sandra E., Gan-Or, Ziv, Keith, Julia, Masellis, Mario, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Calvo, Andrea, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Reijko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hardy, John A., Hodges, Angela K., Love, Seth, McKeith, Ian G., Morris, Christopher M., Morris, Huw R., Palmer, Laura, Pickering-Brown, Stuart, Ryten, Mina, Thomas, Alan J., Troakes, Claire, Albert, Marilyn S., Barrett, Matthew J., Beach, Thomas G., Bekris, Lynn M., Bennett, David A., Boeve, Bradley F., Dawson, Ted M., Dickson, Dennis W., Faber, Kelley, Ferman, Tanis, Ferrucci, Luigi, Flanagan, Margaret E., Foroud, Tatiana M., Ghetti, Bernardino, Gibbs, J. Raphael, Goate, Alison, Goldstein, David S., Graff-Radford, Neill R., Kaufmann, Horacio, Kukull, Walter A., Leverenz, James B., Lopez, Grisel, Mao, Qinwen, Masliah, Eliezer, Monuki, Edwin, Newell, Kathy L., Palma, Jose-Alberto, Perkins, Matthew, Pletnikova, Olga, Renton, Alan E., Resnick, Susan M., Rosenthal, Liana S., Ross, Owen A., Scherzer, Clemens R., Serrano, Geidy E., Shakkottai, Vikram G., Sidransky, Ellen, Tanaka, Toshiko, Tayebi, Nahid, Topol, Eric, Torkamani, Ali, Troncoso, Juan C., Woltjer, Randy, Wszolek, Zbigniew K., Scholz, Sonja W., Baloh, Robert H., Bowser, Robert, Broach, James, Camu, William, Chiò, Adriano, Cooper-Knock, John, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Feldman, Eva, Fratta, Pietro, Gerhard, Glenn, Gibson, Summer B., Glass, Jonathan D., Harms, Matthew B., Heiman-Patterson, Terry D., Jansson, Lilja, Kirby, Janine, Kwan, Justin, Laaksovirta, Hannu, Landers, John E., Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J.L., Maragakis, Nicholas J., Mouzat, Kevin, Myllykangas, Liisa, Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pioro, Erik, Pulst, Stefan M., Ravits, John M., Robberecht, Wim, Rothstein, Jeffrey D., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Stein, Thor, Stone, David J., Tienari, Pentti J., Traynor, Bryan J., Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, Zinman, Lorne, Kaivola, Karri, Chia, Ruth, Ding, Jinhui, Rasheed, Memoona, Fujita, Masashi, Menon, Vilas, Walton, Ronald L., Collins, Ryan L., Billingsley, Kimberley, Brand, Harrison, Talkowski, Michael, Zhao, Xuefang, Dewan, Ramita, Stark, Ali, Ray, Anindita, Solaiman, Sultana, Alvarez Jerez, Pilar, Malik, Laksh, Tienari, Pentti, Mazzini, Letizia, D'Alfonso, Sandra, Moglia, Cristina, and De Jager, Philip L.

Published
2023
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13. β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease

Author

Mittal, Shuchi, Bjørnevik, Kjetil, Im, Doo Soon, Flierl, Adrian, Dong, Xianjun, Locascio, Joseph J, Abo, Kristine M, Long, Elizabeth, Jin, Ming, Xu, Bing, Xiang, Yang K, Rochet, Jean-Christophe, Engeland, Anders, Rizzu, Patrizia, Heutink, Peter, Bartels, Tim, Selkoe, Dennis J, Caldarone, Barbara J, Glicksman, Marcie A, Khurana, Vikram, Schüle, Birgitt, Park, David S, Riise, Trond, and Scherzer, Clemens R

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Neurodegenerative, Biotechnology, Brain Disorders, Aging, Neurosciences, Acquired Cognitive Impairment, Genetics, Parkinson's Disease, Dementia, 2.1 Biological and endogenous factors, Aetiology, Neurological, Acetylation, Adrenergic beta-1 Receptor Agonists, Adrenergic beta-Antagonists, Albuterol, Animals, Cell Line, Tumor, Enhancer Elements, Genetic, Gene Expression Regulation, Histones, Humans, Ligands, Mice, Neuroprotective Agents, Norway, Parkinson Disease, Promoter Regions, Genetic, Propranolol, Receptors, Adrenergic, beta-2, Risk, Substantia Nigra, Transcription, Genetic, alpha-Synuclein, General Science & Technology
Abstract

Copy number mutations implicate excess production of α-synuclein as a possibly causative factor in Parkinson's disease (PD). Using an unbiased screen targeting endogenous gene expression, we discovered that the β2-adrenoreceptor (β2AR) is a regulator of the α-synuclein gene (SNCA). β2AR ligands modulate SNCA transcription through histone 3 lysine 27 acetylation of its promoter and enhancers. Over 11 years of follow-up in 4 million Norwegians, the β2AR agonist salbutamol, a brain-penetrant asthma medication, was associated with reduced risk of developing PD (rate ratio, 0.66; 95% confidence interval, 0.58 to 0.76). Conversely, a β2AR antagonist correlated with increased risk. β2AR activation protected model mice and patient-derived cells. Thus, β2AR is linked to transcription of α-synuclein and risk of PD in a ligand-specific fashion and constitutes a potential target for therapies.

Published
2017

14. Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Author

Adeleye, Adelani, Alba, Camille, Bacikova, Dagmar, Hupalo, Daniel N., Martinez, Elisa McGrath, Pollard, Harvey B., Sukumar, Gauthaman, Soltis, Anthony R., Tuck, Meila, Zhang, Xijun, Wilkerson, Matthew D., Smith, Bradley N., Ticozzi, Nicola, Fallini, Claudia, Gkazi, Athina Soragia, Topp, Simon D., Kost, Jason, Scotter, Emma L., Kenna, Kevin P., Miller, Jack W., Tiloca, Cinzia, Vance, Caroline, Danielson, Eric W., Troakes, Claire, Colombrita, Claudia, Al-Sarraj, Safa, Lewis, Elizabeth A., King, Andrew, Calini, Daniela, Pensato, Viviana, Castellotti, Barbara, de Belleroche, Jacqueline, Baas, Frank, ten Asbroek, Anneloor L.M.A., Sapp, Peter C., McKenna-Yasek, Diane, McLaughlin, Russell L., Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesús, Muñoz-Blanco, José Luis, Stevic, Zorica, D’Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P., Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Diekstra, Frank P., Rademakers, Rosa, van Blitterswijk, Marka, Boylan, Kevin B., Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L., Nicholson, Garth A., Blair, Ian P., Leblond-Manry, Claire, Rouleau, Guy A., Hardiman, Orla, Morrison, Karen E., Veldink, Jan H., van den Berg, Leonard H., Al-Chalabi, Ammar, Pall, Hardev, Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Gellera, Cinzia, Ratti, Antonia, Brown, Robert H., Jr., Shaw, Christopher E., Ambrose, John C., Arumugam, Prabhu, Baple, Emma L., Bleda, Marta, Boardman-Pretty, Freya, Boissiere, Jeanne M., Boustred, Christopher R., Brittain, H., Caulfield, Mark J., Chan, Georgia C., Craig, Clare E.H., Daugherty, Louise C., de Burca, Anna, Devereau, Andrew, Elgar, Greg, Foulger, Rebecca E., Fowler, Tom, Furió-Tarí, Pedro, Hackett, Joanne M., Halai, Dina, Hamblin, Angela, Henderson, Shirley, Holman, James E., Hubbard, Tim J.P., Jackson, Rob, Jones, Louise J., Kasperaviciute, Dalia, Kayikci, Melis, Lahnstein, Lea, Lawson, Kay, Leigh, Sarah E.A., Leong, Ivonne U.S., Lopez, Javier F., Maleady-Crowe, Fiona, Mason, Joanne, McDonagh, Ellen M., Moutsianas, Loukas, Mueller, Michael, Murugaesu, Nirupa, Need, Anna C., Odhams, Chris A., Patch, Christine, Perez-Gil, Daniel, Polychronopoulos, Dimitris, Pullinger, John, Rahim, Tahrima, Rendon, Augusto, Riesgo-Ferreiro, Pablo, Rogers, Tim, Savage, Kevin, Sawant, Kushmita, Scott, Richard H., Siddiq, Afshan, Sieghart, Alexander, Smedley, Damian, Smith, Katherine R., Sosinsky, Alona, Spooner, William, Stevens, Helen E., Stuckey, Alexander, Sultana, Razvan, Thomas, Ellen R.A., Thompson, Simon R., Tregidgo, Carolyn, Walsh, Emma, Watters, Sarah A., Welland, Matthew J., Williams, Eleanor, Witkowska, Katarzyna, Wood, Suzanne M., Zarowiecki, Magdalena, Arepalli, Sampath, Auluck, Pavan, Baloh, Robert H., Bowser, Robert, Brice, Alexis, Broach, James, Camu, William, Chiò, Adriano, Cooper-Knock, John, Corcia, Philippe, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Faghri, Faraz, Farren, Jennifer, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Gerhard, Glenn, Gibson, Summer B., Goutman, Stephen A., Heiman-Patterson, Terry D., Hernandez, Dena G., Hoover, Ben, Jansson, Lilja, Kamel, Freya, Kirby, Janine, Kowall, Neil W., Laaksovirta, Hannu, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel JL., Maragakis, Nicholas J., Mora, Gabriele, Mouzat, Kevin, Myllykangas, Liisa, Nalls, Mike A., Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pioro, Erik, Pulst, Stefan M., Ravits, John M., Renton, Alan E., Robberecht, Wim, Robey, Ian, Rogaeva, Ekaterina, Rothstein, Jeffrey D., Sendtner, Michael, Sidle, Katie C., Simmons, Zachary, Stone, David J., Tienari, Pentti J., Trojanowski, John Q., Troncoso, Juan C., Valori, Miko, Van Damme, Philip, Van Den Bosch, Ludo, Zinman, Lorne, Albani, Diego, Borroni, Barbara, Padovani, Alessandro, Bruni, Amalia, Clarimon, Jordi, Dols-Icardo, Oriol, Illán-Gala, Ignacio, Lleó, Alberto, Danek, Adrian, Galimberti, Daniela, Scarpini, Elio, Serpente, Maria, Graff, Caroline, Chiang, Huei-Hsin, Khoshnood, Behzad, Öijerstedt, Linn, Morris, Christopher M., Nacmias, Benedetta, Sorbi, Sandro, Nielsen, Jorgen E., Hjermind, Lynne E., Novelli, Valeria, Puca, Annibale A., Pastor, Pau, Alvarez, Ignacio, Diez-Fairen, Monica, Aguilar, Miquel, Perneczky, Robert, Diehl-Schimd, Janine, Rossi, Mina, Ruiz, Agustin, Boada, Mercè, Hernández, Isabel, Moreno-Grau, Sonia, Schlachetzki, Johannes C., Aarsland, Dag, Albert, Marilyn S., Attems, Johannes, Barrett, Matthew J., Beach, Thomas G., Bekris, Lynn M., Bennett, David A., Besser, Lilah M., Bigio, Eileen H., Black, Sandra E., Boeve, Bradley F., Bohannan, Ryan C., Brett, Francesca, Brunetti, Maura, Caraway, Chad A., Palma, Jose-Alberto, Calvo, Andrea, Canosa, Antonio, Dickson, Dennis, Duyckaerts, Charles, Faber, Kelley, Ferman, Tanis, Flanagan, Margaret E., Floris, Gianluca, Foroud, Tatiana M., Fortea, Juan, Gan-Or, Ziv, Gentleman, Steve, Ghetti, Bernardino, Gibbs, Jesse Raphael, Goate, Alison, Goldstein, David, González-Aramburu, Isabel, Graff-Radford, Neill R., Hodges, Angela K., Hu, Heng-Chen, Hupalo, Daniel, Infante, Jon, Iranzo, Alex, Kaiser, Scott M., Kaufmann, Horacio, Keith, Julia, Kim, Ronald C., Klein, Gregory, Krüger, Rejko, Kukull, Walter, Kuzma, Amanda, Lage, Carmen, Lesage, Suzanne, Leverenz, James B., Logroscino, Giancarlo, Lopez, Grisel, Love, Seth, Mao, Qinwen, Marti, Maria Jose, Martinez-McGrath, Elisa, Masellis, Mario, Masliah, Eliezer, May, Patrick, McKeith, Ian, Mesulam, Marek-Marsel, Monuki, Edwin S., Newell, Kathy L., Norcliffe-Kaufmann, Lucy, Palmer, Laura, Perkins, Matthew, Pletnikova, Olga, Molina-Porcel, Laura, Reynolds, Regina H., Rodríguez-Rodríguez, Eloy, Rohrer, Jonathan D., Sanchez-Juan, Pascual, Scherzer, Clemens R., Serrano, Geidy E., Shakkottai, Vikram, Sidransky, Ellen, Tayebi, Nahid, Thomas, Alan J., Tilley, Bension S., Walton, Ronald L., Woltjer, Randy, Wszolek, Zbigniew K., Xiromerisiou, Georgia, Zecca, Chiara, Phatnani, Hemali, Kwan, Justin, Sareen, Dhruv, Broach, James R., Arcila-Londono, Ximena, Lee, Edward B., Shneider, Neil A., Fraenkel, Ernest, Zaitlen, Noah, Berry, James D., Malaspina, Andrea, Cox, Gregory A., Thompson, Leslie M., Finkbeiner, Steve, Dardiotis, Efthimios, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos.A., Butovsky, Oleg, Dubnau, Joshua, Nath, Avindra, Harms, Matt, Aronica, Eleonora, Poss, Mary, Phillips-Cremins, Jennifer, Crary, John, Atassi, Nazem, Lange, Dale J., Adams, Darius J., Stefanis, Leonidas, Gotkine, Marc, Babu, Suma, Raj, Towfique, Paganoni, Sabrina, Shalem, Ophir, Smith, Colin, Zhang, Bin, Harris, Brent, Broce, Iris, Drory, Vivian, Ravits, John, McMillan, Corey, Menon, Vilas, Wu, Lani, Altschuler, Steven, Amar, Khaled, Archibald, Neil, Bandmann, Oliver, Capps, Erica, Church, Alistair, Coebergh, Jan, Costantini, Alyssa, Critchley, Peter, Ghosh, Boyd CP., Hu, Michele T.M., Kobylecki, Christopher, Leigh, P. Nigel, Mann, Carl, Massey, Luke A., Morris, Huw R., Nath, Uma, Pavese, Nicola, Paviour, Dominic, Sharma, Jagdish, Vaughan, Jenny, Dewan, Ramita, Chia, Ruth, Ding, Jinhui, Hickman, Richard A., Stein, Thor D., Abramzon, Yevgeniya, Ahmed, Sarah, Sabir, Marya S., Portley, Makayla K., Tucci, Arianna, Ibáñez, Kristina, Shankaracharya, F.N.U., Keagle, Pamela, Rossi, Giacomina, Caroppo, Paola, Tagliavini, Fabrizio, Waldo, Maria L., Johansson, Per M., Nilsson, Christer F., Rowe, James B., Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Jabbari, Edwin, Viollet, Coralie, Glass, Jonathan D., Singleton, Andrew B., Silani, Vincenzo, Ross, Owen A., Ryten, Mina, Torkamani, Ali, Tanaka, Toshiko, Ferrucci, Luigi, Resnick, Susan M., Pickering-Brown, Stuart, Brady, Christopher B., Kowal, Neil, Hardy, John A., Van Deerlin, Vivianna, Vonsattel, Jean Paul, Harms, Matthew B., Ferrari, Raffaele, Landers, John E., Gibbs, J. Raphael, Dalgard, Clifton L., Scholz, Sonja W., and Traynor, Bryan J.

Published
2021
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15. Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson’s disease

Author

Liu, Ganqiang, Peng, Jiajie, Liao, Zhixiang, Locascio, Joseph J., Corvol, Jean-Christophe, Zhu, Frank, Dong, Xianjun, Maple-Grødem, Jodi, Campbell, Meghan C., Elbaz, Alexis, Lesage, Suzanne, Brice, Alexis, Mangone, Graziella, Growdon, John H., Hung, Albert Y., Schwarzschild, Michael A., Hayes, Michael T., Wills, Anne-Marie, Herrington, Todd M., Ravina, Bernard, Shoulson, Ira, Taba, Pille, Kõks, Sulev, Beach, Thomas G., Cormier-Dequaire, Florence, Alves, Guido, Tysnes, Ole-Bjørn, Perlmutter, Joel S., Heutink, Peter, Amr, Sami S., van Hilten, Jacobus J., Kasten, Meike, Mollenhauer, Brit, Trenkwalder, Claudia, Klein, Christine, Barker, Roger A., Williams-Gray, Caroline H., Marinus, Johan, and Scherzer, Clemens R.

Published
2021
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16. 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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17. Prediction of cognition in Parkinson's disease with a clinical–genetic score: a longitudinal analysis of nine cohorts

Author

Scherzer, Clemens R., Hyman, Bradley T., Ivinson, Adrian J., Trisini-Lipsanopoulos, Ana, Franco, Daly, Burke, Kyle, Sudarsky, Lewis R., Hayes, Michael T., Umeh, Chizoba C., Sperling, Reisa, Growdon, John H., Schwarzschild, Michael A., Hung, Albert Y., Flaherty, Alice W., Blacker, Deborah, Wills, Anne-Marie, Sohur, U. Shivraj, Mejia, Nicte I., Viswanathan, Anand, Gomperts, Stephen N., Khurana, Vikram, Albers, Mark W., Alora-Palli, Maria, McGinnis, Scott, Sharma, Nutan, Dickerson, Bradford, Frosch, Matthew, Gomez-Isla, Teresa, Greenberg, Steven, Gusella, James, Hedden, Trey, Hedley-Whyte, E Tessa, Koenig, Aaron, Marquis-Sayagues, Marta, Marshall, Gad, Okereke, Olivia, Stemmer-Rachaminov, Anat, Kloppenburg, Jessica, Schlossmacher, Michael G., Selkoe, Dennis J., Yi, Thomas, Locascio, Joseph J., Li, Haining, Stalberg, Gabriel, Liao, Zhixiang, Barker, Roger, Foltynie, Tom, Williams-Gray, Caroline, Robbins, Trevor, Brayne, Carol, Mason, Sarah, Winder-Rhodes, Sophie, Breen, David P, Cummins, Gemma, Evans, Jonathan, van Hilten, Jacobus J., Marinus, Johan, Corvol, Jean-Christophe, Brice, Alexis, Elbaz, Alexis, Mallet, Alain, Vidailhet, Marie, Bonnet, Anne-Marie, Bonnet, Cecilia, Grabli, David, Hartmann, Andreas, Klebe, Stephan, Lacomblez, Lucette, Mangone, Graziella, Bourdain, Frédéric, Brandel, Jean-Philippe, Derkinderen, Pascal, Durif, Franck, Mesnage, Valérie, Pico, Fernando, Rascol, Olivier, Brefel-Courbon, Christine, Ory-Magne, Fabienne, Forlani, Sylvie, Lesage, Suzanne, Tahiri, Khadija, Albin, Roger, Alcalay, Roy, Ascherio, Alberto, Bowman, Dubois, Chen-Plotkin, Alice, Dawson, Ted, Dewey, Richard, German, Dwight, Saunders-Pullman, Rachel, Scherzer, Clemens, Vaillancourt, David, Petyuk, Vladislav, West, Andy, Zhang, Jing, Liu, Ganqiang, Locascio, Joseph J, Boot, Brendon, Page, Kara, Jansen, Iris E, Tanner, Caroline M, Lang, Anthony E, Eberly, Shirley, Ravina, Bernard, Shoulson, Ira, Cormier-Dequaire, Florence, Heutink, Peter, van Hilten, Jacobus J, Barker, Roger A, Williams-Gray, Caroline H, and Scherzer, Clemens R

Published
2017
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18. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

Author

Chia, Ruth, Sabir, Marya S., Bandres-Ciga, Sara, Saez-Atienzar, Sara, Reynolds, Regina H., Gustavsson, Emil, Walton, Ronald L., Ahmed, Sarah, Viollet, Coralie, Ding, Jinhui, Makarious, Mary B., Diez-Fairen, Monica, Portley, Makayla K., Shah, Zalak, Abramzon, Yevgeniya, Hernandez, Dena G., Blauwendraat, Cornelis, Stone, David J., Eicher, John, Parkkinen, Laura, Ansorge, Olaf, Clark, Lorraine, Honig, Lawrence S., Marder, Karen, Lemstra, Afina, St George-Hyslop, Peter, Londos, Elisabet, Morgan, Kevin, Lashley, Tammaryn, Warner, Thomas T., Jaunmuktane, Zane, Galasko, Douglas, Santana, Isabel, Tienari, Pentti J., Myllykangas, Liisa, Oinas, Minna, Cairns, Nigel J., Morris, John C., Halliday, Glenda M., Van Deerlin, Vivianna M., Trojanowski, John Q., Grassano, Maurizio, Calvo, Andrea, Mora, Gabriele, Canosa, Antonio, Floris, Gianluca, Bohannan, Ryan C., Brett, Francesca, Gan-Or, Ziv, Geiger, Joshua T., Moore, Anni, May, Patrick, Krüger, Rejko, Goldstein, David S., Lopez, Grisel, Tayebi, Nahid, Sidransky, Ellen, Norcliffe-Kaufmann, Lucy, Palma, Jose-Alberto, Kaufmann, Horacio, Shakkottai, Vikram G., Perkins, Matthew, Newell, Kathy L., Gasser, Thomas, Schulte, Claudia, Landi, Francesco, Salvi, Erika, Cusi, Daniele, Masliah, Eliezer, Kim, Ronald C., Caraway, Chad A., Monuki, Edwin S., Brunetti, Maura, Dawson, Ted M., Rosenthal, Liana S., Albert, Marilyn S., Pletnikova, Olga, Troncoso, Juan C., Flanagan, Margaret E., Mao, Qinwen, Bigio, Eileen H., Rodríguez-Rodríguez, Eloy, Infante, Jon, Lage, Carmen, González-Aramburu, Isabel, Sanchez-Juan, Pascual, Ghetti, Bernardino, Keith, Julia, Black, Sandra E., Masellis, Mario, Rogaeva, Ekaterina, Duyckaerts, Charles, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Barrett, Matthew J., Tilley, Bension S., Gentleman, Steve, Logroscino, Giancarlo, Serrano, Geidy E., Beach, Thomas G., McKeith, Ian G., Thomas, Alan J., Attems, Johannes, Morris, Christopher M., Palmer, Laura, Love, Seth, Troakes, Claire, Al-Sarraj, Safa, Hodges, Angela K., Aarsland, Dag, Klein, Gregory, Kaiser, Scott M., Woltjer, Randy, Pastor, Pau, Bekris, Lynn M., Leverenz, James B., Besser, Lilah M., Kuzma, Amanda, Renton, Alan E., Goate, Alison, Bennett, David A., Scherzer, Clemens R., Morris, Huw R., Ferrari, Raffaele, Albani, Diego, Pickering-Brown, Stuart, Faber, Kelley, Kukull, Walter A., Morenas-Rodriguez, Estrella, Lleó, Alberto, Fortea, Juan, Alcolea, Daniel, Clarimon, Jordi, Nalls, Mike A., Ferrucci, Luigi, Resnick, Susan M., Tanaka, Toshiko, Foroud, Tatiana M., Graff-Radford, Neill R., Wszolek, Zbigniew K., Ferman, Tanis, Boeve, Bradley F., Hardy, John A., Topol, Eric J., Torkamani, Ali, Singleton, Andrew B., Ryten, Mina, Dickson, Dennis W., Chiò, Adriano, Ross, Owen A., Gibbs, J. Raphael, Dalgard, Clifton L., Traynor, Bryan J., and Scholz, Sonja W.

Published
2021
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20. A systems-biology approach connects aging mechanisms with Alzheimer’s disease pathogenesis

Author

Leventhal, Matthew J, primary, Zanella, Camila A, additional, Kang, Byunguk, additional, Peng, Jiajie, additional, Gritsch, David, additional, Liao, Zhixiang, additional, Bukhari, Hassan, additional, Wang, Tao, additional, Pao, Ping-Chieh, additional, Danquah, Serwah, additional, Benetatos, Joseph, additional, Nehme, Ralda, additional, Farhi, Samouil, additional, Tsai, Li-Huei, additional, Dong, Xianjun, additional, Scherzer, Clemens R, additional, Feany, Mel B, additional, and Fraenkel, Ernest, additional

Published
2024
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21. Deep sequencing of proteotoxicity modifier genes uncovers a Presenilin-2/beta-amyloid-actin genetic risk module shared among alpha-synucleinopathies

Author

Nazeen, Sumaiya, primary, Wang, Xinyuan, additional, Zielinski, Dina, additional, Lam, Isabel, additional, Hallacli, Erinc, additional, Xu, Ping, additional, Ethier, Elizabeth, additional, Strom, Ronya, additional, Zanella, Camila A., additional, Nithianandam, Vanitha, additional, Ritter, Dylan, additional, Henderson, Alexander, additional, Saurat, Nathalie, additional, Afroz, Jalwa, additional, Nutter-Upham, Andrew, additional, Benyamini, Hadar, additional, Copty, Joseph, additional, Ravishankar, Shyamsundar, additional, Morrow, Autumn, additional, Mitchel, Jonathan, additional, Neavin, Drew, additional, Gupta, Renuka, additional, Farbehi, Nona, additional, Grundman, Jennifer, additional, Myers, Richard H., additional, Scherzer, Clemens R., additional, Trojanowski, John Q., additional, Van Deerlin, Vivianna M., additional, Cooper, Antony A., additional, Lee, Edward B., additional, Erlich, Yaniv, additional, Lindquist, Susan, additional, Peng, Jian, additional, Geschwind, Daniel H, additional, Powell, Joseph, additional, Studer, Lorenz, additional, Feany, Mel B., additional, Sunyaev, Shamil R., additional, and Khurana, Vikram, additional

Published
2024
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22. Venglustat in GBA1-related Parkinson's disease – Authors' reply

Author

Sardi, S Pablo, primary, Giladi, Nir, additional, Alcalay, Roy N, additional, Cuer, Gary, additional, Gasser, Thomas, additional, Gurevich, Tanya, additional, Höglinger, Günter U, additional, Marek, Kenneth, additional, PaccheE, Claudio, additional, Schapira, Anthony H V, additional, Scherzer, Clemens R, additional, Simuni, Tanya, additional, Minini, Pascal, additional, and Peterschmi, M Judith, additional

Published
2024
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27. β-Glucocerebrosidase activity in GBA-linked Parkinson disease: The type of mutation matters

Author

Huh, Young Eun, Chiang, Ming Sum Ruby, Locascio, Joseph J., Liao, Zhixiang, Liu, Ganqiang, Choudhury, Karbi, Kuras, Yuliya I., Tuncali, Idil, Videnovic, Aleksandar, Hunt, Ann L., Schwarzschild, Michael A., Hung, Albert Y., Herrington, Todd M., Hayes, Michael T., Hyman, Bradley T., Wills, Anne-Marie, Gomperts, Stephen N., Growdon, John H., Sardi, Sergio Pablo, and Scherzer, Clemens R.

Published
2020
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29. Genetic risk of Parkinson disease and progression: An analysis of 13 longitudinal cohorts

Author

Iwaki, Hirotaka, Blauwendraat, Cornelis, Leonard, Hampton L., Liu, Ganqiang, Maple-Grødem, Jodi, Corvol, Jean-Christophe, Pihlstrøm, Lasse, van Nimwegen, Marlies, Hutten, Samantha J., Nguyen, Khanh-Dung H., Rick, Jacqueline, Eberly, Shirley, Faghri, Faraz, Auinger, Peggy, Scott, Kirsten M., Wijeyekoon, Ruwani, Van Deerlin, Vivianna M., Hernandez, Dena G., Day-Williams, Aaron G., Brice, Alexis, Alves, Guido, Noyce, Alastair J., Tysnes, Ole-Bjørn, Evans, Jonathan R., Breen, David P., Estrada, Karol, Wegel, Claire E., Danjou, Fabrice, Simon, David K., Ravina, Bernard, Toft, Mathias, Heutink, Peter, Bloem, Bastiaan R., Weintraub, Daniel, Barker, Roger A., Williams-Gray, Caroline H., van de Warrenburg, Bart P., Van Hilten, Jacobus J., Scherzer, Clemens R., Singleton, Andrew B., and Nalls, Mike A.

Published
2019
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30. Publisher Correction: Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease

Author

Dong, Xianjun, Liao, Zhixiang, Gritsch, David, Hadzhiev, Yavor, Bai, Yunfei, Locascio, Joseph J., Guennewig, Boris, Liu, Ganqiang, Blauwendraat, Cornelis, Wang, Tao, Adler, Charles H., Hedreen, John C., Faull, Richard L. M., Frosch, Matthew P., Nelson, Peter T., Rizzu, Patrizia, Cooper, Antony A., Heutink, Peter, Beach, Thomas G., Mattick, John S., Müller, Ferenc, and Scherzer, Clemens R.

Published
2019
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31. Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease

Author

Dong, Xianjun, Liao, Zhixiang, Gritsch, David, Hadzhiev, Yavor, Bai, Yunfei, Locascio, Joseph J., Guennewig, Boris, Liu, Ganqiang, Blauwendraat, Cornelis, Wang, Tao, Adler, Charles H., Hedreen, John C., Faull, Richard L. M., Frosch, Matthew P., Nelson, Peter T., Rizzu, Patrizia, Cooper, Antony A., Heutink, Peter, Beach, Thomas G., Mattick, John S., Müller, Ferenc, and Scherzer, Clemens R.

Published
2018
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32. Mitochondrial haplogroups and cognitive progression in Parkinson's disease

Author

Liu, Ganqiang, Ni, Chunming, Zhan, Jiamin, Li, Weimin, Luo, Junfeng, Liao, Zhixiang, Locascio, Joseph J, Xian, Wenbiao, Chen, Ling, Pei, Zhong, Corvol, Jean-Christophe, Maple-Grødem, Jodi, Campbell, Meghan C, Elbaz, Alexis, Lesage, Suzanne, Brice, Alexis, Hung, Albert Y, Schwarzschild, Michael A, Hayes, Michael T, Wills, Anne-Marie, Ravina, Bernard, Shoulson, Ira, Taba, Pille, Kõks, Sulev, Beach, Thomas G, Cormier-Dequaire, Florence, Alves, Guido, Tysnes, Ole-Bjørn, Perlmutter, Joel S, Heutink, Peter, Van Hilten, Jacobus J, Barker, Roger A, Williams-Gray, Caroline H, Scherzer, Clemens R, International Genetics Of Parkinson Disease Progression (IGPP) Consortium, Liu, Ganqiang [0000-0002-1921-9542], Pei, Zhong [0000-0002-8425-2867], Elbaz, Alexis [0000-0001-9724-5490], Apollo - University of Cambridge Repository, Liu, Ganqiang, Valentino, Rebecca R, Peng, Jiajie, Liao, Zhixiang, Locascio, Joseph J, Corvol, Jean-Christophe, Dong, Xianjun, Maple-Grødem, Jodi, Campbell, Meghan C, Elbaz, Alexis, Lesage, Suzanne, Brice, Alexis, Mangone, Graziella, Growdon, John H, Hung, Albert Y, Schwarzchild, Michael A, Hayes, Michael T, Wills, Anne-Marie, Herrington, Todd M, Ravian, Bernard, Shoulson, Ira, Taba, Pille, Kõks, Sulev, Beach, Thomas G, Cormier-Dequaire, Florence, Alves, Guido, Tysnes, Ole-Bjørn, Perlmutter, Joel S, Heutink, Peter, van Hilten, Jacobus J, Kasten, Meike, Mollenhauer, Brit, Trenkwalder, Claudia, Klein, Christine, Barker, Roger A, Williams-Gray, Caroline H, Marinus, Johan, and Scherzer, Clemens R

Subjects
mitochondrial haplogroups, Parkinson's disease, cognitive progression, Parkinson Disease, genetics [DNA, Mitochondrial], DNA, Mitochondrial, Mitochondria, Cognition, Haplotypes, genetics [Parkinson Disease], Report, Parkinson’s disease, Disease Progression, Humans, Neurology (clinical), ddc:610, epidemiology [Parkinson Disease], genetics [Mitochondria]
Abstract

Liu et al. report that specific mitochondrial haplogroups are associated with the progression of cognitive decline in patients with Parkinson's disease, but not with the progression of motor impairment. Mitochondrial haplotypes may thus be useful for stratifying patients according to their risk of cognitive decline.Mitochondria are a culprit in the onset of Parkinson's disease, but their role during disease progression is unclear. Here we used Cox proportional hazards models to exam the effect of variation in the mitochondrial genome on longitudinal cognitive and motor progression over time in 4064 patients with Parkinson's disease. Mitochondrial macro-haplogroup was associated with reduced risk of cognitive disease progression in the discovery and replication population. In the combined analysis, patients with the super macro-haplogroup J, T, U-# had a 41% lower risk of cognitive progression with P = 2.42 x 10(-6) compared to those with macro-haplogroup H. Exploratory analysis indicated that the common mitochondrial DNA variant, m.2706A>G, was associated with slower cognitive decline with a hazard ratio of 0.68 (95% confidence interval 0.56-0.81) and P = 2.46 x 10(-5). Mitochondrial haplogroups were not appreciably linked to motor progression. This initial genetic survival study of the mitochondrial genome suggests that mitochondrial haplogroups may be associated with the pace of cognitive progression in Parkinson's disease over time.

Published
2023
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33. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Luxembourg Institute of Health - LIH [research center], Fonds National de la Recherche - FnR [sponsor], Kaivola, Karri, Chia, Ruth, Ding, Jinhui, Rasheed, Memoona, Fujita, Masashi, Menon, Vilas, Walton, Ronald L., Collins, Ryan L., Billingsley, Kimberley, Brand, Harrison, Talkowski, Michael, Zhao, Xuefang, Dewan, Ramita, Stark, Ali, Ray, Anindita, Solaiman, Sultana, Alvarez Jerez, Pilar, Malik, Laksh, Dawson, Ted M., Rosenthal, Liana S., Albert, Marilyn S., Pletnikova, Olga, Troncoso, Juan C., Masellis, Mario, Keith, Julia, Black, Sandra E., Ferrucci, Luigi, Resnick, Susan M., Tanaka, Toshiko, Topol, Eric, Torkamani, Ali, Tienari, Pentti, Foroud, Tatiana M., Ghetti, Bernardino, Landers, John E., Ryten, Mina, Morris, Huw R., Hardy, John A., Mazzini, Letizia, D'Alfonso, Sandra, Moglia, Cristina, Calvo, Andrea, Serrano, Geidy E., Beach, Thomas G., Ferman, Tanis, Graff-Radford, Neill R., Boeve, Bradley F., Wszolek, Zbigniew K., Dickson, Dennis W., Chiò, Adriano, Bennett, David A., De Jager, Philip L., Ross, Owen A., Dalgard, Clifton L., Gibbs, J. Raphael, Traynor, Bryan J., Scholz, Sonja W., Soltis, Anthony R., Viollet, Coralie, Sukumar, Gauthaman, Alba, Camille, Lott, Nathaniel, McGrath Martinez, Elisa, Tuck, Meila, Singh, Jatinder, Bacikova, Dagmar, Zhang, Xijun, Hupalo, Daniel N., Adeleye, Adelani, Wilkerson, Matthew D., Pollard, Harvey B., Gan-Or, Ziv, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Rejko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hodges, Angela K., Love, Seth, McKeith, Ian G., Morris, Christopher M., Palmer, Laura, Pickering-Brown, Stuart, Thomas, Alan J., Troakes, Claire, Barrett, Matthew J., Bekris, Lynn M., Faber, Kelley, Flanagan, Margaret E., Goate, Alison, Goldstein, David S., Kaufmann, Horacio, Kukull, Walter A., Leverenz, James B., Lopez, Grisel, Mao, Qinwen, Masliah, Eliezer, Monuki, Edwin, Newell, Kathy L., Palma, Jose-Alberto, Perkins, Matthew, Renton, Alan E., Scherzer, Clemens R., Shakkottai, Vikram G., Sidransky, Ellen, Tayebi, Nahid, Woltjer, Randy, Baloh, Robert H., Bowser, Robert, Broach, James, Camu, William, Cooper-Knock, John, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Feldman, Eva, Fratta, Pietro, Gerhard, Glenn, Gibson, Summer B., Glass, Jonathan D., Harms, Matthew B., Heiman-Patterson, Terry D., Jansson, Lilja, Kirby, Janine, Kwan, Justin, Laaksovirta, Hannu, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J. L., Maragakis, Nicholas J., Mouzat, Kevin, Myllykangas, Liisa, Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pioro, Erik, Pulst, Stefan M., Ravits, John M., Robberecht, Wim, Rothstein, Jeffrey D., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Stein, Thor, Stone, David J., Tienari, Pentti J., Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, Zinman, Lorne, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Luxembourg Institute of Health - LIH [research center], Fonds National de la Recherche - FnR [sponsor], Kaivola, Karri, Chia, Ruth, Ding, Jinhui, Rasheed, Memoona, Fujita, Masashi, Menon, Vilas, Walton, Ronald L., Collins, Ryan L., Billingsley, Kimberley, Brand, Harrison, Talkowski, Michael, Zhao, Xuefang, Dewan, Ramita, Stark, Ali, Ray, Anindita, Solaiman, Sultana, Alvarez Jerez, Pilar, Malik, Laksh, Dawson, Ted M., Rosenthal, Liana S., Albert, Marilyn S., Pletnikova, Olga, Troncoso, Juan C., Masellis, Mario, Keith, Julia, Black, Sandra E., Ferrucci, Luigi, Resnick, Susan M., Tanaka, Toshiko, Topol, Eric, Torkamani, Ali, Tienari, Pentti, Foroud, Tatiana M., Ghetti, Bernardino, Landers, John E., Ryten, Mina, Morris, Huw R., Hardy, John A., Mazzini, Letizia, D'Alfonso, Sandra, Moglia, Cristina, Calvo, Andrea, Serrano, Geidy E., Beach, Thomas G., Ferman, Tanis, Graff-Radford, Neill R., Boeve, Bradley F., Wszolek, Zbigniew K., Dickson, Dennis W., Chiò, Adriano, Bennett, David A., De Jager, Philip L., Ross, Owen A., Dalgard, Clifton L., Gibbs, J. Raphael, Traynor, Bryan J., Scholz, Sonja W., Soltis, Anthony R., Viollet, Coralie, Sukumar, Gauthaman, Alba, Camille, Lott, Nathaniel, McGrath Martinez, Elisa, Tuck, Meila, Singh, Jatinder, Bacikova, Dagmar, Zhang, Xijun, Hupalo, Daniel N., Adeleye, Adelani, Wilkerson, Matthew D., Pollard, Harvey B., Gan-Or, Ziv, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Rejko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hodges, Angela K., Love, Seth, McKeith, Ian G., Morris, Christopher M., Palmer, Laura, Pickering-Brown, Stuart, Thomas, Alan J., Troakes, Claire, Barrett, Matthew J., Bekris, Lynn M., Faber, Kelley, Flanagan, Margaret E., Goate, Alison, Goldstein, David S., Kaufmann, Horacio, Kukull, Walter A., Leverenz, James B., Lopez, Grisel, Mao, Qinwen, Masliah, Eliezer, Monuki, Edwin, Newell, Kathy L., Palma, Jose-Alberto, Perkins, Matthew, Renton, Alan E., Scherzer, Clemens R., Shakkottai, Vikram G., Sidransky, Ellen, Tayebi, Nahid, Woltjer, Randy, Baloh, Robert H., Bowser, Robert, Broach, James, Camu, William, Cooper-Knock, John, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Feldman, Eva, Fratta, Pietro, Gerhard, Glenn, Gibson, Summer B., Glass, Jonathan D., Harms, Matthew B., Heiman-Patterson, Terry D., Jansson, Lilja, Kirby, Janine, Kwan, Justin, Laaksovirta, Hannu, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J. L., Maragakis, Nicholas J., Mouzat, Kevin, Myllykangas, Liisa, Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pioro, Erik, Pulst, Stefan M., Ravits, John M., Robberecht, Wim, Rothstein, Jeffrey D., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Stein, Thor, Stone, David J., Tienari, Pentti J., Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, and Zinman, Lorne

Abstract

We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer’s dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequence data from 5,213 European-ancestry cases and 4,132 controls. We discovered, replicated, and validated a deletion in TPCN1 as a novel risk locus for LBD and detected the known structural variants at the C9orf72 and MAPT loci as associated with FTD/ALS. We also identified rare pathogenic structural variants in both LBD and FTD/ALS. Finally, we assembled a catalog of structural variants that can be mined for new insights into the pathogenesis of these understudied forms of dementia.

Published
2023

35. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias

Author

Kaivola, Karri, primary, Chia, Ruth, additional, Ding, Jinhui, additional, Rasheed, Memoona, additional, Fujita, Masashi, additional, Menon, Vilas, additional, Walton, Ronald L., additional, Collins, Ryan L., additional, Billingsley, Kimberley, additional, Brand, Harrison, additional, Talkowski, Michael, additional, Zhao, Xuefang, additional, Dewan, Ramita, additional, Stark, Ali, additional, Ray, Anindita, additional, Solaiman, Sultana, additional, Alvarez Jerez, Pilar, additional, Malik, Laksh, additional, Dawson, Ted M., additional, Rosenthal, Liana S., additional, Albert, Marilyn S., additional, Pletnikova, Olga, additional, Troncoso, Juan C., additional, Masellis, Mario, additional, Keith, Julia, additional, Black, Sandra E., additional, Ferrucci, Luigi, additional, Resnick, Susan M., additional, Tanaka, Toshiko, additional, Topol, Eric, additional, Torkamani, Ali, additional, Tienari, Pentti, additional, Foroud, Tatiana M., additional, Ghetti, Bernardino, additional, Landers, John E., additional, Ryten, Mina, additional, Morris, Huw R., additional, Hardy, John A., additional, Mazzini, Letizia, additional, D'Alfonso, Sandra, additional, Moglia, Cristina, additional, Calvo, Andrea, additional, Serrano, Geidy E., additional, Beach, Thomas G., additional, Ferman, Tanis, additional, Graff-Radford, Neill R., additional, Boeve, Bradley F., additional, Wszolek, Zbigniew K., additional, Dickson, Dennis W., additional, Chiò, Adriano, additional, Bennett, David A., additional, De Jager, Philip L., additional, Ross, Owen A., additional, Dalgard, Clifton L., additional, Gibbs, J. Raphael, additional, Traynor, Bryan J., additional, Scholz, Sonja W., additional, Soltis, Anthony R., additional, Viollet, Coralie, additional, Sukumar, Gauthaman, additional, Alba, Camille, additional, Lott, Nathaniel, additional, McGrath Martinez, Elisa, additional, Tuck, Meila, additional, Singh, Jatinder, additional, Bacikova, Dagmar, additional, Zhang, Xijun, additional, Hupalo, Daniel N., additional, Adeleye, Adelani, additional, Wilkerson, Matthew D., additional, Pollard, Harvey B., additional, Gan-Or, Ziv, additional, Rogaeva, Ekaterina, additional, Brice, Alexis, additional, Lesage, Suzanne, additional, Xiromerisiou, Georgia, additional, Canosa, Antonio, additional, Chio, Adriano, additional, Logroscino, Giancarlo, additional, Mora, Gabriele, additional, Krüger, Reijko, additional, May, Patrick, additional, Alcolea, Daniel, additional, Clarimon, Jordi, additional, Fortea, Juan, additional, Gonzalez-Aramburu, Isabel, additional, Infante, Jon, additional, Lage, Carmen, additional, Lleó, Alberto, additional, Pastor, Pau, additional, Sanchez-Juan, Pascual, additional, Brett, Francesca, additional, Aarsland, Dag, additional, Al-Sarraj, Safa, additional, Attems, Johannes, additional, Gentleman, Steve, additional, Hodges, Angela K., additional, Love, Seth, additional, McKeith, Ian G., additional, Morris, Christopher M., additional, Palmer, Laura, additional, Pickering-Brown, Stuart, additional, Thomas, Alan J., additional, Troakes, Claire, additional, Barrett, Matthew J., additional, Bekris, Lynn M., additional, Faber, Kelley, additional, Flanagan, Margaret E., additional, Goate, Alison, additional, Goldstein, David S., additional, Kaufmann, Horacio, additional, Kukull, Walter A., additional, Leverenz, James B., additional, Lopez, Grisel, additional, Mao, Qinwen, additional, Masliah, Eliezer, additional, Monuki, Edwin, additional, Newell, Kathy L., additional, Palma, Jose-Alberto, additional, Perkins, Matthew, additional, Renton, Alan E., additional, Scherzer, Clemens R., additional, Shakkottai, Vikram G., additional, Sidransky, Ellen, additional, Tayebi, Nahid, additional, Woltjer, Randy, additional, Baloh, Robert H., additional, Bowser, Robert, additional, Broach, James, additional, Camu, William, additional, Cooper-Knock, John, additional, Drepper, Carsten, additional, Drory, Vivian E., additional, Dunckley, Travis L., additional, Feldman, Eva, additional, Fratta, Pietro, additional, Gerhard, Glenn, additional, Gibson, Summer B., additional, Glass, Jonathan D., additional, Harms, Matthew B., additional, Heiman-Patterson, Terry D., additional, Jansson, Lilja, additional, Kirby, Janine, additional, Kwan, Justin, additional, Laaksovirta, Hannu, additional, Landi, Francesco, additional, Le Ber, Isabelle, additional, Lumbroso, Serge, additional, MacGowan, Daniel J.L., additional, Maragakis, Nicholas J., additional, Mouzat, Kevin, additional, Myllykangas, Liisa, additional, Orrell, Richard W., additional, Ostrow, Lyle W., additional, Pamphlett, Roger, additional, Pioro, Erik, additional, Pulst, Stefan M., additional, Ravits, John M., additional, Robberecht, Wim, additional, Rothstein, Jeffrey D., additional, Sendtner, Michael, additional, Shaw, Pamela J., additional, Sidle, Katie C., additional, Simmons, Zachary, additional, Stein, Thor, additional, Stone, David J., additional, Tienari, Pentti J., additional, Valori, Miko, additional, Van Damme, Philip, additional, Van Deerlin, Vivianna M., additional, Van Den Bosch, Ludo, additional, and Zinman, Lorne, additional

Published
2023
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37. Plasma biomarkers for diagnosis of Alzheimer's disease and prediction of cognitive decline in individuals with mild cognitive impairment

Author

Kivisäkk, Pia, primary, Carlyle, Becky C., additional, Sweeney, Thadryan, additional, Trombetta, Bianca A., additional, LaCasse, Kathryn, additional, El-Mufti, Leena, additional, Tuncali, Idil, additional, Chibnik, Lori B., additional, Das, Sudeshna, additional, Scherzer, Clemens R., additional, Johnson, Keith A., additional, Dickerson, Bradford C., additional, Gomez-Isla, Teresa, additional, Blacker, Deborah, additional, Oakley, Derek H., additional, Frosch, Matthew P., additional, Hyman, Bradley T., additional, Aghvanyan, Anahit, additional, Bathala, Pradeepthi, additional, Campbell, Christopher, additional, Sigal, George, additional, Stengelin, Martin, additional, and Arnold, Steven E., additional

Published
2023
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39. Correction to: Clinical trial-ready patient cohorts for multiple system atrophy: coupling biospecimen and iPSC banking to longitudinal deep-phenotyping

Author

Ndayisaba, Alain, primary, Pitaro, Ariana T., additional, Willett, Andrew S., additional, Jones, Kristie A., additional, de Gusmao, Claudio Melo, additional, Olsen, Abby L., additional, Kim, Jisoo, additional, Rissanen, Eero, additional, Woods, Jared K., additional, Srinivasan, Sharan R., additional, Nagy, Anna, additional, Nagy, Amanda, additional, Mesidor, Merlyne, additional, Cicero, Steven, additional, Patel, Viharkumar, additional, Oakley, Derek H., additional, Tuncali, Idil, additional, Taglieri-Noble, Katherine, additional, Clark, Emily C., additional, Paulson, Jordan, additional, Krolewski, Richard C., additional, Ho, Gary P., additional, Hung, Albert Y., additional, Wills, Anne-Marie, additional, Hayes, Michael T., additional, Macmore, Jason P., additional, Warren, Luigi, additional, Bower, Pamela G., additional, Langer, Carol B., additional, Kellerman, Lawrence R., additional, Humphreys, Christopher W., additional, Glanz, Bonnie I., additional, Dielubanza, Elodi J., additional, Frosch, Matthew P., additional, Freeman, Roy L., additional, Gibbons, Christopher H., additional, Stefanova, Nadia, additional, Chitnis, Tanuja, additional, Weiner, Howard L., additional, Scherzer, Clemens R., additional, Scholz, Sonja W., additional, Vuzman, Dana, additional, Cox, Laura M., additional, Wenning, Gregor, additional, Schmahmann, Jeremy D., additional, Gupta, Anoopum S., additional, Novak, Peter, additional, Young, Geoffrey S., additional, Feany, Mel B., additional, Singhal, Tarun, additional, and Khurana, Vikram, additional

Published
2022
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40. Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping

Author

Ndayisaba, Alain, primary, Pitaro, Ariana T., additional, Willett, Andrew S., additional, Jones, Kristie A., additional, de Gusmao, Claudio Melo, additional, Olsen, Abby L., additional, Kim, Jisoo, additional, Rissanen, Eero, additional, Woods, Jared K., additional, Srinivasan, Sharan R., additional, Nagy, Anna, additional, Nagy, Amanda, additional, Mesidor, Merlyne, additional, Cicero, Steven, additional, Patel, Viharkumar, additional, Oakley, Derek H., additional, Tuncali, Idil, additional, Taglieri-Noble, Katherine, additional, Clark, Emily C., additional, Paulson, Jordan, additional, Krolewski, Richard C., additional, Ho, Gary P., additional, Hung, Albert Y., additional, Wills, Anne-Marie, additional, Hayes, Michael T., additional, Macmore, Jason P., additional, Warren, Luigi, additional, Bower, Pamela G., additional, Langer, Carol B., additional, Kellerman, Lawrence R., additional, Humphreys, Christopher W., additional, Glanz, Bonnie I., additional, Dielubanza, Elodi J., additional, Frosch, Matthew P., additional, Freeman, Roy L., additional, Gibbons, Christopher H., additional, Stefanova, Nadia, additional, Chitnis, Tanuja, additional, Weiner, Howard L., additional, Scherzer, Clemens R., additional, Scholz, Sonja W., additional, Vuzman, Dana, additional, Cox, Laura M., additional, Wenning, Gregor, additional, Schmahmann, Jeremy D., additional, Gupta, Anoopum S., additional, Novak, Peter, additional, Young, Geoffrey S., additional, Feany, Mel B., additional, Singhal, Tarun, additional, and Khurana, Vikram, additional

Published
2022
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42. <scp> GBA </scp> and <scp> APOE </scp> Impact Cognitive Decline in Parkinson's Disease: A 10‐Year Population‐Based Study

Author

Szwedo, Aleksandra A, Dalen, Ingvild, Pedersen, Kenn Freddy, Camacho, Marta, Bäckström, David, Forsgren, Lars, Tzoulis, Charalampos, Winder‐Rhodes, Sophie, Hudson, Gavin, Liu, Ganqiang, Scherzer, Clemens R, Lawson, Rachael A, Yarnall, Alison J, Williams‐Gray, Caroline H, Macleod, Angus D, Counsell, Carl E, Tysnes, Ole‐Bjørn, Alves, Guido, Maple‐Grødem, Jodi, Camacho, Marta [0000-0002-1490-5703], Liu, Ganqiang [0000-0002-1921-9542], Williams‐Gray, Caroline H [0000-0002-2648-9743], Macleod, Angus D [0000-0002-6284-4239], Maple‐Grødem, Jodi [0000-0001-7142-0078], and Apollo - University of Cambridge Repository

Subjects
RESEARCH ARTICLE, Parkinson's disease, GBA, cognitive decline, APOE, RESEARCH ARTICLES, dementia
Abstract

Background: Common genetic variance in apolipoprotein E (APOE), β‐glucocerebrosidase (GBA), microtubule‐associated protein tau (MAPT), and α‐synuclein (SNCA) has been linked to cognitive decline in Parkinson’s disease (PD), although studies have yielded mixed results. Objectives: To evaluate the effect of genetic variants in APOE, GBA, MAPT, and SNCA on cognitive decline and risk of dementia in a pooled analysis of six longitudinal, non‐selective, population‐based cohorts of newly diagnosed PD patients. Methods: 1002 PD patients, followed for up to 10 years (median 7.2 years), were genotyped for at least one of APOE ‐ε4, GBA mutations, MAPT H1/H2, or SNCA rs356219. We evaluated the effect of genotype on the rate of cognitive decline (Mini‐Mental State Examanation, MMSE) using linear mixed models and the development of dementia (diagnosed using standardized criteria) using Cox regression; multiple comparisons were accounted for using Benjamini−Hochberg corrections. Results: Carriers of APOE‐ε4 (n = 281, 29.7%) and GBA mutations (n = 100, 10.3%) had faster cognitive decline and were at higher risk of progression to dementia (APOE‐ε4, HR 3.57, P < 0.001; GBA mutations, HR 1.76, P = 0.001) than non‐carriers. The risk of cognitive decline and dementia (HR 5.19, P < 0.001) was further increased in carriers of both risk genotypes (n = 23). No significant effects were observed for MAPT or SNCA rs356219. Conclusions: GBA and APOE genotyping could improve the prediction of cognitive decline in PD, which is important to inform the clinical trial selection and potentially to enable personalized treatment © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Published
2022

44. GBA and APOE impact cognitive decline in Parkinson's disease : A 10-year population-based study

Author

Szwedo, Aleksandra A, Dalen, Ingvild, Pedersen, Kenn Freddy, Camacho, Marta, Bäckström, David C, Forsgren, Lars, Tzoulis, Charalampos, Winder-Rhodes, Sophie, Hudson, Gavin, Liu, Ganqiang, Scherzer, Clemens R, Lawson, Rachael A, Yarnall, Alison J, Williams-Gray, Caroline H, Macleod, Angus D, Counsell, Carl E, Tysnes, Ole-Bjørn, Alves, Guido, Maple-Grødem, Jodi, Szwedo, Aleksandra A, Dalen, Ingvild, Pedersen, Kenn Freddy, Camacho, Marta, Bäckström, David C, Forsgren, Lars, Tzoulis, Charalampos, Winder-Rhodes, Sophie, Hudson, Gavin, Liu, Ganqiang, Scherzer, Clemens R, Lawson, Rachael A, Yarnall, Alison J, Williams-Gray, Caroline H, Macleod, Angus D, Counsell, Carl E, Tysnes, Ole-Bjørn, Alves, Guido, and Maple-Grødem, Jodi

Published
2022
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45. Proteome profiling of cerebrospinal fluid reveals biomarker candidates for Parkinson's disease

Author

Karayel, Ozge, Virreira Winter, Sebastian, Padmanabhan, Shalini, Kuras, Yuliya I., Vu, Duc Tung, Tuncali, Idil, Merchant, Kalpana, Wills, Anne Marie, Scherzer, Clemens R., Mann, Matthias, Karayel, Ozge, Virreira Winter, Sebastian, Padmanabhan, Shalini, Kuras, Yuliya I., Vu, Duc Tung, Tuncali, Idil, Merchant, Kalpana, Wills, Anne Marie, Scherzer, Clemens R., and Mann, Matthias

Abstract

Parkinson's disease (PD) is a growing burden worldwide, and there is no reliable biomarker used in clinical routines to date. Cerebrospinal fluid (CSF) is routinely collected in patients with neurological symptoms and should closely reflect alterations in PD patients’ brains. Here, we describe a scalable and sensitive mass spectrometry (MS)-based proteomics workflow for CSF proteome profiling. From two independent cohorts with over 200 individuals, our workflow reproducibly quantifies over 1,700 proteins from minimal CSF amounts. Machine learning determines OMD, CD44, VGF, PRL, and MAN2B1 to be altered in PD patients or to significantly correlate with clinical scores. We also uncover signatures of enhanced neuroinflammation in LRRK2 G2019S carriers, as indicated by increased levels of CTSS, PLD4, and HLA proteins. A comparison with our previously acquired urinary proteomes reveals a large overlap in PD-associated changes, including lysosomal proteins, opening up new avenues to improve our understanding of PD pathogenesis.

Published
2022

48. Plasma biomarkers for prognosis of cognitive decline in patients with mild cognitive impairment

Author

Kivisäkk, Pia, primary, Magdamo, Colin, additional, Trombetta, Bianca A, additional, Noori, Ayush, additional, Kuo, Yi kai E, additional, Chibnik, Lori B, additional, Carlyle, Becky C, additional, Serrano-Pozo, Alberto, additional, Scherzer, Clemens R, additional, Hyman, Bradley T, additional, Das, Sudeshna, additional, and Arnold, Steven E, additional

Published
2022
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50. Plasma biomarkers for diagnosis of Alzheimer's disease and prediction of cognitive decline in individuals with mild cognitive impairment

Author

Kivisakk, Pia, primary, Sweeney, Thadryan, additional, Carlyle, Becky C, additional, Trombetta, Bianca A, additional, LaCasse, Kathryn, additional, El-Mufti, Leena, additional, Tuncali, Idil, additional, Chibnik, Lori B, additional, Das, Sudeshna, additional, Scherzer, Clemens R, additional, Johnson, Keith A, additional, Dickerson, Bradford C, additional, Gomez-Isla, Teresa, additional, Blacker, Deborah, additional, Oakley, Derek H, additional, Frosch, Matthew P, additional, Hyman, Bradley T, additional, Aghvanyan, Anahit, additional, Bathala, Pradeepthi, additional, Campbell, Christopher, additional, Sigal, George, additional, Stengelin, Martin, additional, and Arnold, Steven E, additional

Published
2022
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