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787 results on '"Serrano, Geidy E."'

1. A cross-disease resource of living human microglia identifies disease-enriched subsets and tool compounds recapitulating microglial states

Author

Tuddenham, John F., Taga, Mariko, Haage, Verena, Marshe, Victoria S., Roostaei, Tina, White, Charles, Lee, Annie J., Fujita, Masashi, Khairallah, Anthony, Zhang, Ya, Green, Gilad, Hyman, Bradley, Frosch, Matthew, Hopp, Sarah, Beach, Thomas G., Serrano, Geidy E., Corboy, John, Habib, Naomi, Klein, Hans-Ulrich, Soni, Rajesh Kumar, Teich, Andrew F., Hickman, Richard A., Alcalay, Roy N., Shneider, Neil, Schneider, Julie, Sims, Peter A., Bennett, David A., Olah, Marta, Menon, Vilas, and De Jager, Philip L.

Published
2024
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2. [18F]Flotaza for Aβ Plaque Diagnostic Imaging: Evaluation in Postmortem Human Alzheimer’s Disease Brain Hippocampus and PET/CT Imaging in 5xFAD Transgenic Mice

Author

Sandhu, Yasmin K, Bath, Harman S, Shergill, Jasmine, Liang, Christopher, Syed, Amina U, Ngo, Allyson, Karim, Fariha, Serrano, Geidy E, Beach, Thomas G, and Mukherjee, Jogeshwar

Subjects
Biochemistry and Cell Biology, Biological Sciences, Medicinal and Biomolecular Chemistry, Chemical Sciences, Microbiology, Neurodegenerative, Aging, Alzheimer's Disease, Neurosciences, Dementia, Brain Disorders, Bioengineering, Biomedical Imaging, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Brain, Hippocampus, Animals, Mice, Transgenic, Humans, Mice, Alzheimer Disease, Disease Models, Animal, Fluorine Radioisotopes, Pyridines, Pyrrolidinones, Radiopharmaceuticals, Autopsy, Aged, Aged, 80 and over, Female, Male, Plaque, Amyloid, Positron Emission Tomography Computed Tomography, 5xFAD transgenic mice, Alzheimer’s disease, PET imaging, [18F]flotaza, hippocampus, human Aβ plaques, Other Chemical Sciences, Genetics, Other Biological Sciences, Chemical Physics, Biochemistry and cell biology, Medicinal and biomolecular chemistry
Abstract

The diagnostic value of imaging Aβ plaques in Alzheimer's disease (AD) has accelerated the development of fluorine-18 labeled radiotracers with a longer half-life for easier translation to clinical use. We have developed [18F]flotaza, which shows high binding to Aβ plaques in postmortem human AD brain slices with low white matter binding. We report the binding of [18F]flotaza in postmortem AD hippocampus compared to cognitively normal (CN) brains and the evaluation of [18F]flotaza in transgenic 5xFAD mice expressing Aβ plaques. [18F]Flotaza binding was assessed in well-characterized human postmortem brain tissue sections consisting of HP CA1-subiculum (HP CA1-SUB) regions in AD (n = 28; 13 male and 15 female) and CN subjects (n = 32; 16 male and 16 female). Adjacent slices were immunostained with anti-Aβ and analyzed using QuPath. In vitro and in vivo [18F]flotaza PET/CT studies were carried out in 5xFAD mice. Post-mortem human brain slices from all AD subjects were positively IHC stained with anti-Aβ. High [18F]flotaza binding was measured in the HP CA1-SUB grey matter (GM) regions compared to white matter (WM) of AD subjects with GM/WM > 100 in some subjects. The majority of CN subjects had no decipherable binding. Male AD exhibited greater WM than AD females (AD WM♂/WM♀ > 5; p < 0.001) but no difference amongst CN WM. In vitro studies in 5xFAD mice brain slices exhibited high binding [18F]flotaza ratios (>50 versus cerebellum) in the cortex, HP, and thalamus. In vivo, PET [18F]flotaza exhibited binding to Aβ plaques in 5xFAD mice with SUVR~1.4. [18F]Flotaza is a new Aβ plaque PET imaging agent that exhibited high binding to Aβ plaques in postmortem human AD. Along with the promising results in 5xFAD mice, the translation of [18F]flotaza to human PET studies may be worthwhile.

Published
2024

3. Identification of isoAsp7-Aβ as a major Aβ variant in Alzheimer’s disease, dementia with Lewy bodies and vascular dementia

Author

Schrempel, Sarah, Kottwitz, Anna Katharina, Piechotta, Anke, Gnoth, Kathrin, Büschgens, Luca, Hartlage-Rübsamen, Maike, Morawski, Markus, Schenk, Mathias, Kleinschmidt, Martin, Serrano, Geidy E., Beach, Thomas G., Rostagno, Agueda, Ghiso, Jorge, Heneka, Michael T., Walter, Jochen, Wirths, Oliver, Schilling, Stephan, and Roßner, Steffen

Published
2024
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4. Correction: Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy

Author

Wang, Hui, Chang, Timothy S., Dombroski, Beth A., Cheng, Po-Liang, Patil, Vishakha, Valiente-Banuet, Leopoldo, Farrell, Kurt, Mclean, Catriona, Molina-Porcel, Laura, Rajput, Alex, De Deyn, Peter Paul, Le Bastard, Nathalie, Gearing, Marla, Kaat, Laura Donker, Van Swieten, John C., Dopper, Elise, Ghetti, Bernardino F., Newell, Kathy L., Troakes, Claire, de Yébenes, Justo G., Rábano-Gutierrez, Alberto, Meller, Tina, Oertel, Wolfgang H., Respondek, Gesine, Stamelou, Maria, Arzberger, Thomas, Roeber, Sigrun, Müller, Ulrich, Hopfner, Franziska, Pastor, Pau, Brice, Alexis, Durr, Alexandra, Le Ber, Isabelle, Beach, Thomas G., Serrano, Geidy E., Hazrati, Lili-Naz, Litvan, Irene, Rademakers, Rosa, Ross, Owen A., Galasko, Douglas, Boxer, Adam L., Miller, Bruce L., Seeley, Willian W., Van Deerlin, Vivanna M., Lee, Edward B., White, III, Charles L., Morris, Huw, de Silva, Rohan, Crary, John F., Goate, Alison M., Friedman, Jeffrey S., Leung, Yuk Yee, Coppola, Giovanni, Naj, Adam C., Wang, Li-San, Dalgard, Clifton, Dickson, Dennis W., Höglinger, Günter U., Schellenberg, Gerard D., Geschwind, Daniel H., and Lee, Wan-Ping

Published
2024
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5. Neuronal BAG3 attenuates tau hyperphosphorylation, synaptic dysfunction, and cognitive deficits induced by traumatic brain injury via the regulation of autophagy-lysosome pathway

Author

Sweeney, Nicholas, Kim, Tae Yeon, Morrison, Cody T., Li, Liangping, Acosta, Diana, Liang, Jiawen, Datla, Nithin V., Fitzgerald, Julie A., Huang, Haoran, Liu, Xianglan, Tan, Gregory Huang, Wu, Min, Karelina, Kate, Bray, Chelsea E., Weil, Zachary M., Scharre, Douglas W., Serrano, Geidy E., Saito, Takashi, Saido, Takaomi C., Beach, Thomas G., Kokiko-Cochran, Olga N., Godbout, Jonathan P., Johnson, Gail V. W., and Fu, Hongjun

Published
2024
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7. Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy

Author

Wang, Hui, Chang, Timothy S., Dombroski, Beth A., Cheng, Po-Liang, Patil, Vishakha, Valiente-Banuet, Leopoldo, Farrell, Kurt, Mclean, Catriona, Molina-Porcel, Laura, Rajput, Alex, De Deyn, Peter Paul, Le Bastard, Nathalie, Gearing, Marla, Kaat, Laura Donker, Van Swieten, John C., Dopper, Elise, Ghetti, Bernardino F., Newell, Kathy L., Troakes, Claire, de Yébenes, Justo G., Rábano-Gutierrez, Alberto, Meller, Tina, Oertel, Wolfgang H., Respondek, Gesine, Stamelou, Maria, Arzberger, Thomas, Roeber, Sigrun, Müller, Ulrich, Hopfner, Franziska, Pastor, Pau, Brice, Alexis, Durr, Alexandra, Le Ber, Isabelle, Beach, Thomas G., Serrano, Geidy E., Hazrati, Lili-Naz, Litvan, Irene, Rademakers, Rosa, Ross, Owen A., Galasko, Douglas, Boxer, Adam L., Miller, Bruce L., Seeley, Willian W., Van Deerlin, Vivanna M., Lee, Edward B., White, III, Charles L., Morris, Huw, de Silva, Rohan, Crary, John F., Goate, Alison M., Friedman, Jeffrey S., Leung, Yuk Yee, Coppola, Giovanni, Naj, Adam C., Wang, Li-San, Dalgard, Clifton, Dickson, Dennis W., Höglinger, Günter U., Schellenberg, Gerard D., Geschwind, Daniel H., and Lee, Wan-Ping

Published
2024
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11. Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology

Author

Mastenbroek, Sophie E., Vogel, Jacob W., Collij, Lyduine E., Serrano, Geidy E., Tremblay, Cécilia, Young, Alexandra L., Arce, Richard A., Shill, Holly A., Driver-Dunckley, Erika D., Mehta, Shyamal H., Belden, Christine M., Atri, Alireza, Choudhury, Parichita, Barkhof, Frederik, Adler, Charles H., Ossenkoppele, Rik, Beach, Thomas G., and Hansson, Oskar

Published
2024
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14. Differential methylation analysis in neuropathologically confirmed dementia with Lewy bodies

Author

Reho, Paolo, Saez-Atienzar, Sara, Ruffo, Paola, Solaiman, Sultana, Shah, Zalak, Chia, Ruth, Kaivola, Karri, Traynor, Bryan J., Tilley, Bension S., Gentleman, Steve M., Hodges, Angela K., Aarsland, Dag, Monuki, Edwin S., Newell, Kathy L., Woltjer, Randy, Albert, Marilyn S., Dawson, Ted M., Rosenthal, Liana S., Troncoso, Juan C., Pletnikova, Olga, Serrano, Geidy E., Beach, Thomas G., Easwaran, Hariharan P., and Scholz, Sonja W.

Published
2024
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15. TREM1 disrupts myeloid bioenergetics and cognitive function in aging and Alzheimer disease mouse models

Author

Wilson, Edward N., Wang, Congcong, Swarovski, Michelle S., Zera, Kristy A., Ennerfelt, Hannah E., Wang, Qian, Chaney, Aisling, Gauba, Esha, Ramos Benitez, Javier A., Le Guen, Yann, Minhas, Paras S., Panchal, Maharshi, Tan, Yuting J., Blacher, Eran, A. Iweka, Chinyere, Cropper, Haley, Jain, Poorva, Liu, Qingkun, Mehta, Swapnil S., Zuckerman, Abigail J., Xin, Matthew, Umans, Jacob, Huang, Jolie, Durairaj, Aarooran S., Serrano, Geidy E., Beach, Thomas G., Greicius, Michael D., James, Michelle L., Buckwalter, Marion S., McReynolds, Melanie R., Rabinowitz, Joshua D., and Andreasson, Katrin I.

Published
2024
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16. Biochemical analyses of tau and other neuronal markers in the submandibular gland and frontal cortex across stages of Alzheimer disease

Author

Hamsafar, Yamah, Chen, Qian, Borowsky, Alexander D, Beach, Thomas G, Serrano, Geidy E, Sue, Lucia I, Adler, Charles H, Walker, Douglas G, and Dugger, Brittany N

Subjects
Biochemistry and Cell Biology, Biological Sciences, Neurosciences, Alzheimer's Disease, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Brain Disorders, Neurodegenerative, Aging, 2.1 Biological and endogenous factors, Neurological, Humans, Alzheimer Disease, Submandibular Gland, tau Proteins, Neurofibrillary Tangles, Neurons, Frontal Lobe, Phosphorylation, Submandibular gland, Big tau, 4a exon, Tau, Phosphorylated tau, Tyrosine hydroxylase, Neurofilament heavy chain, Microtubule-associated protein 2, Psychology, Cognitive Sciences, Biochemistry and cell biology, Biological psychology
Abstract

Hyperphosphorylation of the microtubule-associated protein tau is hypothesized to lead to the development of neurofibrillary tangles in select brain regions during normal aging and in Alzheimer disease (AD). The distribution of neurofibrillary tangles is staged by its involvement starting in the transentorhinal regions of the brain and in final stages progress to neocortices. However, it has also been determined neurofibrillary tangles can extend into the spinal cord and select tau species are found in peripheral tissues and this may be depended on AD disease stage. To further understand the relationships of peripheral tissues to AD, we utilized biochemical methods to evaluate protein levels of total tau and phosphorylated tau (p-tau) as well as other neuronal proteins (i.e., tyrosine hydroxylase (TH), neurofilament heavy chain (NF-H), and microtubule-associated protein 2 (MAP2)) in the submandibular gland and frontal cortex of human cases across different clinicopathological stages of AD (n = 3 criteria not met or low, n = 6 intermediate, and n = 9 high likelihood that dementia is due to AD based on National Institute on Aging-Reagan criteria). We report differential protein levels based on the stage of AD, anatomic specific tau species, as well as differences in TH and NF-H. In addition, exploratory findings were made of the high molecular weight tau species big tau that is unique to peripheral tissues. Although sample sizes were small, these findings are, to our knowledge, the first comparison of these specific protein changes in these tissues.

Published
2023

17. APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia

Author

Haney, Michael S., Pálovics, Róbert, Munson, Christy Nicole, Long, Chris, Johansson, Patrik K., Yip, Oscar, Dong, Wentao, Rawat, Eshaan, West, Elizabeth, Schlachetzki, Johannes C. M., Tsai, Andy, Guldner, Ian Hunter, Lamichhane, Bhawika S., Smith, Amanda, Schaum, Nicholas, Calcuttawala, Kruti, Shin, Andrew, Wang, Yung-Hua, Wang, Chengzhong, Koutsodendris, Nicole, Serrano, Geidy E., Beach, Thomas G., Reiman, Eric M., Glass, Christopher K., Abu-Remaileh, Monther, Enejder, Annika, Huang, Yadong, and Wyss-Coray, Tony

Published
2024
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18. 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

20. Genome sequence analyses identify novel risk loci for multiple system atrophy

Author

Chia, Ruth, Ray, Anindita, Shah, Zalak, Ding, Jinhui, Ruffo, Paola, Fujita, Masashi, Menon, Vilas, Saez-Atienzar, Sara, Reho, Paolo, Kaivola, Karri, Walton, Ronald L., Reynolds, Regina H., Karra, Ramita, Sait, Shaimaa, Akcimen, Fulya, Diez-Fairen, Monica, Alvarez, Ignacio, Fanciulli, Alessandra, Stefanova, Nadia, Seppi, Klaus, Duerr, Susanne, Leys, Fabian, Krismer, Florian, Sidoroff, Victoria, Zimprich, Alexander, Pirker, Walter, Rascol, Olivier, Foubert-Samier, Alexandra, Meissner, Wassilios G., Tison, François, Pavy-Le Traon, Anne, Pellecchia, Maria Teresa, Barone, Paolo, Russillo, Maria Claudia, Marín-Lahoz, Juan, Kulisevsky, Jaime, Torres, Soraya, Mir, Pablo, Periñán, Maria Teresa, Proukakis, Christos, Chelban, Viorica, Wu, Lesley, Goh, Yee Y., Parkkinen, Laura, Hu, Michele T., Kobylecki, Christopher, Saxon, Jennifer A., Rollinson, Sara, Garland, Emily, Biaggioni, Italo, Litvan, Irene, Rubio, Ileana, Alcalay, Roy N., Kwei, Kimberly T., Lubbe, Steven J., Mao, Qinwen, Flanagan, Margaret E., Castellani, Rudolph J., Khurana, Vikram, Ndayisaba, Alain, Calvo, Andrea, Mora, Gabriele, Canosa, Antonio, Floris, Gianluca, Bohannan, Ryan C., Moore, Anni, Norcliffe-Kaufmann, Lucy, Palma, Jose-Alberto, Kaufmann, Horacio, Kim, Changyoun, Iba, Michiyo, Masliah, Eliezer, Dawson, Ted M., Rosenthal, Liana S., Pantelyat, Alexander, Albert, Marilyn S., Pletnikova, Olga, Troncoso, Juan C., Infante, Jon, Lage, Carmen, Sánchez-Juan, Pascual, Serrano, Geidy E., Beach, Thomas G., Pastor, Pau, Morris, Huw R., Albani, Diego, Clarimon, Jordi, Wenning, Gregor K., Hardy, John A., Ryten, Mina, Topol, Eric, Torkamani, Ali, Chiò, Adriano, Bennett, David A., De Jager, Philip L., Low, Philip A., Singer, Wolfgang, Cheshire, William P., Wszolek, Zbigniew K., Dickson, Dennis W., Traynor, Bryan J., Gibbs, J. Raphael, Dalgard, Clifton L., Ross, Owen A., Houlden, Henry, and Scholz, Sonja W.

Published
2024
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22. MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study

Author

Warner, Thomas T, Jaunmuktane, Zane, Boeve, Bradley F, Duara, Ranjan, Graff-Radford, Neill R, Josephs, Keith A, Knopman, David S, Koga, Shunsuke, Murray, Melissa E, Lyons, Kelly E, Pahwa, Rajesh, Petersen, Ronald C, Whitwell, Jennifer L, Grinberg, Lea T, Miller, Bruce, Schlereth, Athena, Spina, Salvatore, Grossman, Murray, Irwin, David J, Suh, EunRan, Trojanowski, John Q, Van Deerlin, Vivianna M, Wolk, David A, Connors, Theresa R, Dooley, Patrick M, Oakley, Derek H, Aldecoa, Iban, Balasa, Mircea, Gelpi, Ellen, Borrego-Écija, Sergi, Gascon-Bayarri, Jordi, Sánchez-Valle, Raquel, Sanz-Cartagena, Pilar, Piñol-Ripoll, Gerard, Bigio, Eileen H, Flanagan, Margaret E, Rogalski, Emily J, Weintraub, Sandra, Schneider, Julie A, Peng, Lihua, Zhu, Xiongwei, Chang, Koping, Troncoso, Juan C, Prokop, Stefan, Newell, Kathy L, Jones, Matthew, Richardson, Anna, Roncaroli, Federico, Snowden, Julie, Allinson, Kieren, Singh, Poonam, Serrano, Geidy E, Flowers, Xena E, Goldman, James E, Heaps, Allison C, Leskinen, Sandra P, Black, Sandra E, Masellis, Mario, King, Andrew, Al-Sarraj, Safa, Troakes, Claire, Hodges, John R, Kril, Jillian J, Kwok, John B, Piguet, Olivier, Roeber, Sigrun, Attems, Johannes, Thomas, Alan J, Evers, Bret M., Bieniek, Kevin F, Sieben, Anne A, Cras, Patrick P, De Vil, Bart B, Bird, Thomas, Castellani, Rudolph J, Chaffee, Ann, Franklin, Erin, Haroutunian, Vahram, Jacobsen, Max, Keene, Dirk, Latimer, Caitlin S, Metcalf, Jeff, Perrin, Richard J, Purohit, Dushyant P, Rissman, Robert A, Schantz, Aimee, Walker, Jamie, De Deyn, Peter P, Duyckaerts, Charles, Le Ber, Isabelle, Seilhean, Danielle, Turbant-Leclere, Sabrina, Ervin, John F, Nennesmo, Inger, Riehl, James, Nacmias, Benedetta, Finger, Elizabeth C, Blauwendraat, Cornelis, Nalls, Mike A, Singleton, Andrew B, Vitale, Dan, Cunha, Cristina, Wszolek, Zbigniew K, Valentino, Rebecca R, Scotton, William J, Roemer, Shanu F, Lashley, Tammaryn, Heckman, Michael G, Shoai, Maryam, Martinez-Carrasco, Alejandro, Tamvaka, Nicole, Walton, Ronald L, Baker, Matthew C, Macpherson, Hannah L, Real, Raquel, Soto-Beasley, Alexandra I, Mok, Kin, Revesz, Tamas, Christopher, Elizabeth A, DeTure, Michael, Seeley, William W, Lee, Edward B, Frosch, Matthew P, Molina-Porcel, Laura, Gefen, Tamar, Redding-Ochoa, Javier, Ghetti, Bernardino, Robinson, Andrew C, Kobylecki, Christopher, Rowe, James B, Beach, Thomas G, Teich, Andrew F, Keith, Julia L, Bodi, Istvan, Halliday, Glenda M, Gearing, Marla, Arzberger, Thomas, Morris, Christopher M, White, Charles L, 3rd, Mechawar, Naguib, Boluda, Susana, MacKenzie, Ian R, McLean, Catriona, Cykowski, Matthew D, Wang, Shih-Hsiu J, Graff, Caroline, Nagra, Rashed M, Kovacs, Gabor G, Giaccone, Giorgio, Neumann, Manuela, Ang, Lee-Cyn, Carvalho, Agostinho, Morris, Huw R, Rademakers, Rosa, Hardy, John A, Dickson, Dennis W, Rohrer, Jonathan D, and Ross, Owen A

Published
2024
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23. A Novel Tissue Atlas and Online Tool for the Interrogation of Small RNA Expression in Human Tissues and Biofluids

Author

Alsop, Eric, Meechoovet, Bessie, Kitchen, Robert, Sweeney, Thadryan, Beach, Thomas G, Serrano, Geidy E, Hutchins, Elizabeth, Ghiran, Ionita, Reiman, Rebecca, Syring, Michael, Hsieh, Michael, Courtright-Lim, Amanda, Valkov, Nedyalka, Whitsett, Timothy G, Rakela, Jorge, Pockros, Paul, Rozowsky, Joel, Gallego, Juan, Huentelman, Matthew J, Shah, Ravi, Nakaji, Peter, Kalani, M Yashar S, Laurent, Louise, Das, Saumya, and Van Keuren-Jensen, Kendall

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biotechnology, Genetics, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Generic health relevance, cerebrospinal fluid, extracellular RNA, extracellular vesicle, plasma, saliva, small RNA, tissue atlas, urine, Biological sciences, Biomedical and clinical sciences
Abstract

One promising goal for utilizing the molecular information circulating in biofluids is the discovery of clinically useful biomarkers. Extracellular RNAs (exRNAs) are one of the most diverse classes of molecular cargo, easily assayed by sequencing and with expressions that rapidly change in response to subject status. Despite diverse exRNA cargo, most evaluations from biofluids have focused on small RNA sequencing and analysis, specifically on microRNAs (miRNAs). Another goal of characterizing circulating molecular information, is to correlate expression to injuries associated with specific tissues of origin. Biomarker candidates are often described as being specific, enriched in a particular tissue or associated with a disease process. Likewise, miRNA data is often reported to be specific, enriched for a tissue, without rigorous testing to support the claim. Here we provide a tissue atlas of small RNAs from 30 different tissues and three different blood cell types. We analyzed the tissues for enrichment of small RNA sequences and assessed their expression in biofluids: plasma, cerebrospinal fluid, urine, and saliva. We employed published data sets representing physiological (resting vs. acute exercise) and pathologic states (early- vs. late-stage liver fibrosis, and differential subtypes of stroke) to determine differential tissue-enriched small RNAs. We also developed an online tool that provides information about exRNA sequences found in different biofluids and tissues. The data can be used to better understand the various types of small RNA sequences in different tissues as well as their potential release into biofluids, which should help in the validation or design of biomarker studies.

Published
2022

28. Correction to: α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson’s disease from multiple system atrophy

Author

Dutta, Suman, Hornung, Simon, Kruayatidee, Adira, Maina, Katherine N, del Rosario, Irish, Paul, Kimberly C, Wong, Darice Y, Duarte Folle, Aline, Markovic, Daniela, Palma, Jose-Alberto, Serrano, Geidy E, Adler, Charles H, Perlman, Susan L, Poon, Wayne W, Kang, Un Jung, Alcalay, Roy N, Sklerov, Miriam, Gylys, Karen H, Kaufmann, Horacio, Fogel, Brent L, Bronstein, Jeff M, Ritz, Beate, and Bitan, Gal

Subjects
Neurological, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

A correction to this paper has been published: https://doi.org/10.1007/s00401-021-02332-0.

Published
2021

29. α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson’s disease from multiple system atrophy

Author

Dutta, Suman, Hornung, Simon, Kruayatidee, Adira, Maina, Katherine N, del Rosario, Irish, Paul, Kimberly C, Wong, Darice Y, Duarte Folle, Aline, Markovic, Daniela, Palma, Jose-Alberto, Serrano, Geidy E, Adler, Charles H, Perlman, Susan L, Poon, Wayne W, Kang, Un Jung, Alcalay, Roy N, Sklerov, Miriam, Gylys, Karen H, Kaufmann, Horacio, Fogel, Brent L, Bronstein, Jeff M, Ritz, Beate, and Bitan, Gal

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Neurodegenerative, Neurosciences, Parkinson's Disease, Brain Disorders, Aging, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Neurological, Adult, Aged, Aged, 80 and over, Area Under Curve, Biomarkers, Cohort Studies, Diagnosis, Differential, Enzyme-Linked Immunosorbent Assay, Exosomes, Female, Healthy Volunteers, Humans, Immunoprecipitation, Male, Middle Aged, Multiple System Atrophy, Neurons, Oligodendroglia, Parkinson Disease, Reproducibility of Results, Sensitivity and Specificity, alpha-Synuclein, Biomarker, Extracellular vesicles, Synucleinopathy, Biofluid, Neurology & Neurosurgery
Abstract

The diagnosis of Parkinson's disease (PD) and atypical parkinsonian syndromes is difficult due to the lack of reliable, easily accessible biomarkers. Multiple system atrophy (MSA) is a synucleinopathy whose symptoms often overlap with PD. Exosomes isolated from blood by immunoprecipitation using CNS markers provide a window into the brain's biochemistry and may assist in distinguishing between PD and MSA. Thus, we asked whether α-synuclein (α-syn) in such exosomes could distinguish among healthy individuals, patients with PD, and patients with MSA. We isolated exosomes from the serum or plasma of these three groups by immunoprecipitation using neuronal and oligodendroglial markers in two independent cohorts and measured α-syn in these exosomes using an electrochemiluminescence ELISA. In both cohorts, α-syn concentrations were significantly lower in the control group and significantly higher in the MSA group compared to the PD group. The ratio between α-syn concentrations in putative oligodendroglial exosomes compared to putative neuronal exosomes was a particularly sensitive biomarker for distinguishing between PD and MSA. Combining this ratio with the α-syn concentration itself and the total exosome concentration, a multinomial logistic model trained on the discovery cohort separated PD from MSA with an AUC = 0.902, corresponding to 89.8% sensitivity and 86.0% specificity when applied to the independent validation cohort. The data demonstrate that a minimally invasive blood test measuring α-syn in blood exosomes immunoprecipitated using CNS markers can distinguish between patients with PD and patients with MSA with high sensitivity and specificity. Future optimization and validation of the data by other groups would allow this strategy to become a viable diagnostic test for synucleinopathies.

Published
2021

31. 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, and Serrano, Geidy E

Subjects
Biological Sciences, Genetics, Human Genome, Alzheimer's Disease Related Dementias (ADRD), Prevention, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Aging, Dementia, Brain Disorders, Acquired Cognitive Impairment, Lewy Body Dementia, Biotechnology, Parkinson's Disease, Neurosciences, Neurodegenerative, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adaptor Proteins, Signal Transducing, Alzheimer Disease, Case-Control Studies, Gene Expression Profiling, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Glucosylceramidase, Humans, Lewy Body Disease, Nuclear Proteins, Parkinson Disease, Polymorphism, Single Nucleotide, Tumor Suppressor Proteins, alpha-Synuclein, American Genome Center, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.

Published
2021

32. Clinicopathological Correlation: Dopamine and Amyloid PET Imaging with Neuropathology in Three Subjects Clinically Diagnosed with Alzheimer's Disease or Dementia with Lewy Bodies.

Author

Gupta, Harsh V, Beach, Thomas G, Mehta, Shyamal H, Shill, Holly A, Driver-Dunckley, Erika, Sabbagh, Marwan N, Belden, Christine M, Liebsack, Carolyn, Dugger, Brittany N, Serrano, Geidy E, Sue, Lucia I, Siderowf, Andrew, Pontecorvo, Michael J, Mintun, Mark A, Joshi, Abhinay D, and Adler, Charles H

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Alzheimer's Disease, Neurodegenerative, Brain Disorders, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Dementia, Lewy Body Dementia, Biomedical Imaging, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid, Aniline Compounds, Dopamine, Ethylene Glycols, Fatal Outcome, Female, Fluorine Radioisotopes, Humans, Lewy Body Disease, Male, Middle Aged, Plaque, Amyloid, Positron-Emission Tomography, Radiopharmaceuticals, Tetrabenazine, Alzheimer's disease, amyloid, AV-133, dementia with Lewy bodies, synucleinopathy, VMAT2, Alzheimer’s disease, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

BackgroundImaging biomarkers have the potential to distinguish between different brain pathologies based on the type of ligand used with PET. AV-45 PET (florbetapir, Amyvid™) is selective for the neuritic plaque amyloid of Alzheimer's disease (AD), while AV-133 PET (florbenazine) is selective for VMAT2, which is a dopaminergic marker.ObjectiveTo report the clinical, AV-133 PET, AV-45 PET, and neuropathological findings of three clinically diagnosed dementia patients who were part of the Avid Radiopharmaceuticals AV133-B03 study as well as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND).MethodsThree subjects who had PET imaging with both AV-133 and AV-45 as well as a standardized neuropathological assessment were included. The final clinical, PET scan, and neuropathological diagnoses were compared.ResultsThe clinical and neuropathological diagnoses were made blinded to PET scan results. The first subject had a clinical diagnosis of dementia with Lewy bodies (DLB); AV-133 PET showed bilateral striatal dopaminergic degeneration, and AV-45 PET was positive for amyloid. The final clinicopathological diagnosis was DLB and AD. The second subject was diagnosed clinically with probable AD; AV-45 PET was positive for amyloid, while striatal AV-133 PET was normal. The final clinicopathological diagnosis was DLB and AD. The third subject had a clinical diagnosis of DLB. Her AV-45 PET was positive for amyloid and striatal AV-133 showed dopaminergic degeneration. The final clinicopathological diagnosis was multiple system atrophy and AD.ConclusionPET imaging using AV-133 for the assessment of striatal VMAT2 density may help distinguish between AD and DLB. However, some cases of DLB with less-pronounced nigrostriatal dopaminergic neuronal loss may be missed.

Published
2021

34. 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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36. Alzheimer’s disease-associated U1 snRNP splicing dysfunction causes neuronal hyperexcitability and cognitive impairment

Author

Chen, Ping-Chung, Han, Xian, Shaw, Timothy I., Fu, Yingxue, Sun, Huan, Niu, Mingming, Wang, Zhen, Jiao, Yun, Teubner, Brett J. W., Eddins, Donnie, Beloate, Lauren N., Bai, Bing, Mertz, Joseph, Li, Yuxin, Cho, Ji-Hoon, Wang, Xusheng, Wu, Zhiping, Liu, Danting, Poudel, Suresh, Yuan, Zuo-Fei, Mancieri, Ariana, Low, Jonathan, Lee, Hyeong-Min, Patton, Mary H., Earls, Laurie R., Stewart, Elizabeth, Vogel, Peter, Hui, Yawei, Wan, Shibiao, Bennett, David A., Serrano, Geidy E., Beach, Thomas G., Dyer, Michael A., Smeyne, Richard J., Moldoveanu, Tudor, Chen, Taosheng, Wu, Gang, Zakharenko, Stanislav S., Yu, Gang, and Peng, Junmin

Published
2022
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37. Unified Staging System for Lewy Body Disorders: Clinicopathologic Correlations and Comparison to Braak Staging.

Author

Adler, Charles H, Beach, Thomas G, Zhang, Nan, Shill, Holly A, Driver-Dunckley, Erika, Caviness, John N, Mehta, Shyamal H, Sabbagh, Marwan N, Serrano, Geidy E, Sue, Lucia I, Belden, Christine M, Powell, Jessica, Jacobson, Sandra A, Zamrini, Edward, Shprecher, David, Davis, Kathryn J, Dugger, Brittany N, and Hentz, Joseph G

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Dementia, Aging, Neurodegenerative, Clinical Research, Parkinson's Disease, Acquired Cognitive Impairment, Brain Disorders, Neurological, Aged, Aged, 80 and over, Brain, Cognitive Dysfunction, Female, Humans, Lewy Bodies, Lewy Body Disease, Male, Severity of Illness Index, alpha-Synuclein, a-Synuclein, Braak staging system, Dementia with Lewy bodies, Incidental Lewy body disease, Lewy body, Parkinson disease, Unified Staging System for Lewy Body Disorders, Neurology & Neurosurgery, Clinical sciences
Abstract

This study was designed to correlate clinical findings with the extent of pathologic a-synuclein (aSyn) in the brain using the Unified Staging System for Lewy Body disorders (USSLB). Data from 280 cases from the Arizona Study of Aging and Neurodegenerative Disorders are presented. Each case had a complete USSLB staging and at least 1 full research clinical assessment, including subspecialty neurologist-administered movement and cognitive evaluation. Of the 280, 25.7% were cognitively normal, 8.6% had mild cognitive impairment, and 65.7% had dementia. All cases could be categorized into 1 of 5 USSLB stages (8.6% stage I-olfactory bulb only; 15.4% IIa-brainstem predominant; 13.6% IIb-limbic predominant; 31.8% III-brainstem and limbic; and 30.7% IV-neocortical) yet using the Braak staging system 70 cases (25.3%) could not be classified. Those with USSLB stages III and IV died at a younger age. Multiple measures of motor parkinsonism, cognitive impairment, hyposmia, and probable RBD were significantly correlated with increasing USSLB stage. We conclude that the USSLB is the most comprehensive staging system for all Lewy body disorders and allows for categorization and ranking of all brains with significant correlations to many motor and nonmotor clinical signs and symptoms.

Published
2019

38. Tau immunoreactivity in peripheral tissues of human aging and select tauopathies

Author

Dugger, Brittany N, Hoffman, Brittany R, Scroggins, Alex, Serrano, Geidy E, Adler, Charles H, Shill, Holly A, Belden, Christine M, Sabbagh, Marwan N, Caviness, John N, Driver Dunckley, Erika, and Beach, Thomas G

Subjects
Biochemistry and Cell Biology, Biological Sciences, Aging, Brain Disorders, Acquired Cognitive Impairment, Neurosciences, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Immunohistochemistry, Male, Neurofibrillary Tangles, Neurons, Tauopathies, tau Proteins, Propagation, Spread, Submandibular gland, Skin, Colon, AT8, Psychology, Cognitive Sciences, Biochemistry and cell biology, Biological psychology
Abstract

Many studies have been directed at understanding mechanisms of tau aggregation and therapeutics, nearly all focusing on the brain. It is critical to understand the presence of tau in peripheral tissues since this may provide new insights into disease progression and selective vulnerability. The current study sought to determine the presence of select tau species in peripheral tissues in elderly individuals and across an array of tauopathies. Using formalin fixed paraffin embedded sections, we examined abdominal skin, submandibular gland, and sigmoid colon among 69 clinicopathologically defined cases: 19 lacking a clinical neuropathological diagnosis (normal controls), 26 progressive supranuclear palsy (PSP), 21 Alzheimer's disease (AD), and 3 with corticobasal degeneration (CBD). Immunohistochemistry was performed using antibodies for "total" tau (HT7) and two phosphorylated tau species (AT8 and pT231). HT7 staining of abdominal skin revealed immunoreactivity of potential nerve elements in 5% of cases (1 AD, 1 AD/PSP, and 1 CBD out of 55 cases examined); skin sections lacked AT8 and pT231 immunoreactive nerve elements. Submandibular glands from all cases had HT7 immunoreactive nerve elements; while pT231 was present in 92% of cases, and AT8 in only 3 cases (2 AD and one AD/PSP case). In sigmoid colon, HT7 immunoreactivity was present in all but 2 cases (97%), pT231 in 54%, and AT8 was present in only 5/62 cases (8%). These data suggest select tau species in CNS tauopathies do not have a high propensity to spread to the periphery and this may hold clues for the understanding of CNS tau pathogenicity and vulnerability.

Published
2019

39. Wolframin is a novel regulator of tau pathology and neurodegeneration

Author

Chen, Shuo, Acosta, Diana, Li, Liangping, Liang, Jiawen, Chang, Yuzhou, Wang, Cankun, Fitzgerald, Julie, Morrison, Cody, Goulbourne, Chris N., Nakano, Yoshi, Villegas, Nancy C. Hernandez, Venkataraman, Lalitha, Brown, Cris, Serrano, Geidy E., Bell, Erica, Wemlinger, Trina, Wu, Min, Kokiko-Cochran, Olga N., Popovich, Phillip, Flowers, Xena E., Honig, Lawrence S., Vonsattel, Jean Paul, Scharre, Douglas W., Beach, Thomas G., Ma, Qin, Kuret, Jeff, Kõks, Sulev, Urano, Fumihiko, Duff, Karen E., and Fu, Hongjun

Published
2022
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40. Distinct subcellular localization of tau and alpha-synuclein in lewy body disease.

Author

Fischer, D. Luke, Menard, Marissa, Abdelaziz, Omar Z., Kanaan, Nicholas M., Cobbs, Virginia G., Kennedy, Richard E., Serrano, Geidy E., Beach, Thomas G., and Volpicelli-Daley, Laura A.

Subjects
TEMPORAL lobe, NEUROFIBRILLARY tangles, PROTEIN-protein interactions, MEDICAL sciences, ALPHA-synuclein
Abstract

Lewy bodies and neurofibrillary tangles, composed of α-synuclein (α-syn) and tau, respectively, often are found together in the same brain and correlate with worsening cognition. Human postmortem studies show colocalization of α-syn and tau occurs in Lewy bodies, but with limited effort to quantify colocalization. In this study, postmortem middle temporal gyrus tissue from decedents (n = 9) without temporal lobe disease (control) or with Lewy body disease (LBD) was immunofluorescently labeled with antibodies to phosphorylated α-syn (p-α-syn), tau phosphorylated at Ser202/Thr205 (p-tau), or exposure of tau's phosphatase-activating domain (PAD-tau) as a marker of early tau aggregates. Immunofluorescence for major-histocompatibility complex class 2 (MHCII) and ionized calcium binding adaptor molecule 1 (Iba1) also was performed because inflammation is an additional pathological hallmark of LBDs, and they were a positive control for two markers known to colocalize. The abundance of p-α-syn, p-tau, and MHCII was significantly associated with diagnosis of LBD. Quantification of colocalization showed that MHCII and Iba1 colocalized, demonstrating activated immune cells are mostly microglia. However, p-α-syn rarely colocalized with p-tau or PAD-tau, although the overlap of p-α-syn with PAD-tau was significantly associated with LBD. In the rare cases pathologic α-syn and pathologic tau were found in the same Lewy body or Lewy neurite, tau appeared to surround α-syn but did not colocalize within the same structure. The relationship between tau and α-syn copathology is important for explaining clinical symptoms, severity, and progression, but there is no evidence for frequent, direct protein-protein interactions in the middle temporal gyrus. [ABSTRACT FROM AUTHOR]

Published
2025
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41. Biomarker‐Based Approach to α‐Synucleinopathies: Lessons from Neuropathology.

Author

Kovacs, Gabor G., Grinberg, Lea T., Halliday, Glenda, Alafuzoff, Irina, Dugger, Brittany N., Murayama, Shigeo, Forrest, Shelley L., Martinez‐Valbuena, Ivan, Tanaka, Hidetomo, Kon, Tomoya, Yoshida, Koji, Jaunmuktane, Zane, Spina, Salvatore, Nelson, Peter T., Gentleman, Steve, Alegre‐Abarrategui, Javier, Serrano, Geidy E., Paes, Vitor Ribeiro, Takao, Masaki, and Wakabayashi, Koichi

Published
2024
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42. Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination

Author

Röltgen, Katharina, Nielsen, Sandra C.A., Silva, Oscar, Younes, Sheren F., Zaslavsky, Maxim, Costales, Cristina, Yang, Fan, Wirz, Oliver F., Solis, Daniel, Hoh, Ramona A., Wang, Aihui, Arunachalam, Prabhu S., Colburg, Deana, Zhao, Shuchun, Haraguchi, Emily, Lee, Alexandra S., Shah, Mihir M., Manohar, Monali, Chang, Iris, Gao, Fei, Mallajosyula, Vamsee, Li, Chunfeng, Liu, James, Shoura, Massa J., Sindher, Sayantani B., Parsons, Ella, Dashdorj, Naranjargal J., Dashdorj, Naranbaatar D., Monroe, Robert, Serrano, Geidy E., Beach, Thomas G., Chinthrajah, R. Sharon, Charville, Gregory W., Wilbur, James L., Wohlstadter, Jacob N., Davis, Mark M., Pulendran, Bali, Troxell, Megan L., Sigal, George B., Natkunam, Yasodha, Pinsky, Benjamin A., Nadeau, Kari C., and Boyd, Scott D.

Published
2022
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43. Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level

Author

Johnson, Erik C. B., Carter, E. Kathleen, Dammer, Eric B., Duong, Duc M., Gerasimov, Ekaterina S., Liu, Yue, Liu, Jiaqi, Betarbet, Ranjita, Ping, Lingyan, Yin, Luming, Serrano, Geidy E., Beach, Thomas G., Peng, Junmin, De Jager, Philip L., Haroutunian, Vahram, Zhang, Bin, Gaiteri, Chris, Bennett, David A., Gearing, Marla, Wingo, Thomas S., Wingo, Aliza P., Lah, James J., Levey, Allan I., and Seyfried, Nicholas T.

Published
2022
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44. Lewy body pathology in Alzheimer's disease: A clinicopathological prospective study

Author

Savica, Rodolfo, Beach, Thomas G, Hentz, Joseph G, Sabbagh, Marwan N, Serrano, Geidy E, Sue, Lucia I, Dugger, Brittany N, Shill, Holly A, Driver‐Dunckley, Erika, Caviness, John N, Mehta, Shyamal H, Jacobson, Sandra A, Belden, Christine M, Davis, Kathryn J, Zamrini, Edward, Shprecher, David R, and Adler, Charles H

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Dementia, Acquired Cognitive Impairment, Alzheimer's Disease, Neurodegenerative, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Lewy Body Dementia, 2.1 Biological and endogenous factors, Detection, screening and diagnosis, Aetiology, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Databases, Factual, Female, Humans, Lewy Bodies, Male, Neuropsychological Tests, Prospective Studies, Psychiatric Status Rating Scales, Alzheimer's disease, Lewy bodies, neuropsychology, pathology, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveIdentify clinical features predictive of Lewy body pathology in Alzheimer's disease (AD) patients in an ongoing longitudinal clinicopathologic study.Material and methodsWe queried the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) database for dementia cases with AD pathology (1997-2015). Subjects received longitudinal comprehensive clinical evaluations including motor/neuropsychological assessment and Apo-E4 genotyping. All cases were autopsied and had standard neuropathological assessments for AD and Lewy-type synucleinopathy (LTS). Subjects were categorized based on standardized pathological criteria with AD cases that had LTS but did not meet DLB pathologic criteria being categorized as ADLB. We performed pairwise comparison between the different diagnoses and multivariable modelling to identify clinical symptoms that predict the pathological diagnosis.ResultsWe identified 32 DLB/AD, 54 ADLB, 70 AD only and 41 PDD/AD cases. AD subjects with LTS pathology had higher UPDRS II and III total scores as well as generally higher individual scores compared to AD alone. While depression scales and Trail-making Test A correlated significantly with LTS, other neuropsychological variables were not significantly different. Apo E4 occurrence was similar in all groups (40%-49%).ConclusionsOur study suggests that the presence (or absence) of LTS influences motor and non-motor clinical findings in AD patients. These findings may lead to biomarkers that allow for more targeted treatment of AD.

Published
2019

45. Predicting alpha-synuclein pathology by REM sleep behavior disorder diagnosis.

Author

Shprecher, David R, Adler, Charles H, Zhang, Nan, Hentz, Joseph G, Serrano, Geidy E, Dugger, Brittany N, Shill, Holly A, Savica, Rodolfo, Caviness, John N, Sabbagh, Marwan N, Belden, Christine M, Driver-Dunckley, Erika, Mehta, Shyamal H, Sue, Lucia I, Davis, Kathryn J, Zamrini, Edward, and Beach, Thomas G

Subjects
Humans, Lewy Body Disease, Supranuclear Palsy, Progressive, REM Sleep Behavior Disorder, Statistics, Nonparametric, Aged, Aged, 80 and over, Female, Male, alpha-Synuclein, Surveys and Questionnaires, Dementia with Lewy bodies, Parkinson disease, Parkinson disease dementia, REM sleep behavior disorder, Neurosciences, Brain Disorders, Behavioral and Social Science, Parkinson's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Sleep Research, Dementia, Acquired Cognitive Impairment, Neurodegenerative, Aging, Clinical Research, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Neurological, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Inability to accurately diagnose Lewy type alpha-synucleinopathy (LTS) pre-mortem has been a major obstacle to clinical care and research. Probable REM sleep behavior disorder (PRBD) diagnosed with support of instruments such as the Mayo Sleep Questionnaire (MSQ) may provide a cost effective means of predicting LTS. Since 2007, 602 subjects in the Arizona Study of Aging and Neurodegenerative Disorders had clinician assessment for PRBD (298 with, 304 without support of the MSQ), completed cognitive and movement examinations, and had neuropathological assessment. Mean age at death was 84.8 years. Histological evidence of LTS was found in 80/101(79.2%) cases with PRBD and 198/501 (39.5%) without PRBD (p

Published
2018

46. Are Clinical Certainty Ratings Helpful in the Diagnosis of Parkinson's Disease?

Author

Gupta, Harsh V, Mehta, Shyamal H, Zhang, Nan, Hentz, Joseph G, Shill, Holly A, Driver‐Dunckley, Erika, Sabbagh, Marwan N, Belden, Christine M, Dugger, Brittany N, Beach, Thomas G, Serrano, Geidy E, Sue, Lucia I, Davis, Kathryn, and Adler, Charles H

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Aging, Neurosciences, Clinical Research, Parkinson's Disease, Brain Disorders, Neurodegenerative, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Neurological, Parkinson's disease, diagnosis certainty, neuropathology, Clinical sciences
Abstract

BackgroundClinical diagnostic criteria for PD rely on rest tremor, bradykinesia, and rigidity. These features are non-specific and neuropathological confirmation remains the gold standard for diagnosis. This study presents data on clinical certainty ratings in autopsy-proven PD.MethodsSubjects were assessed annually by a movement disorders specialist and assigned to a clinical certainty group for PD based on multiple clinical features before autopsy. The three groups considered for analysis are as follows: Group I 0-49% certainty, Group II 50-89% certainty, and Group III 90-100% certainty. All subjects were autopsied and had a standardized neuropathological assessment.Results275 subjects were assigned a PD certainty at their last visit before death. Group I had 80 subjects, Group II 56 subjects, and Group III 139 subjects. The clinical features recorded in Group I, II, and III, were as follows: rest tremor, bradykinesia, rigidity, postural instability, asymmetric onset, persistent asymmetry, current response to dopaminergic treatment, motor fluctuations, and dyskinesia. Rigidity, postural instability, asymmetric onset, current response to dopaminergic treatment, motor fluctuation, and dyskinesia were more likely to be present in the group which was rated with higher certainty. The final diagnosis of PD was confirmed by neuropathological assessment in 85% of the patients in Group III as compared to 30% in Group II and 5% in Group I.ConclusionsHigh certainty (90-100%) had strong positive predictive value (85%) for autopsy-proven PD as compared to either lower certainty groups (0-49% and 50-89%) which had lower predictive value (5% and 30% respectively).

Published
2018

48. Antemortem detection of Parkinson’s disease pathology in peripheral biopsies using artificial intelligence

Author

Signaevsky, Maxim, Marami, Bahram, Prastawa, Marcel, Tabish, Nabil, Iida, Megan A., Zhang, Xiang Fu, Sawyer, Mary, Duran, Israel, Koenigsberg, Daniel G., Bryce, Clare H., Chahine, Lana M., Mollenhauer, Brit, Mosovsky, Sherri, Riley, Lindsey, Dave, Kuldip D., Eberling, Jamie, Coffey, Chris S., Adler, Charles H., Serrano, Geidy E., White, III, Charles L., Koll, John, Fernandez, Gerardo, Zeineh, Jack, Cordon-Cardo, Carlos, Beach, Thomas G., and Crary, John F.

Published
2022
Full Text
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50. Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease

Author

Chen, Shuo, Chang, Yuzhou, Li, Liangping, Acosta, Diana, Li, Yang, Guo, Qi, Wang, Cankun, Turkes, Emir, Morrison, Cody, Julian, Dominic, Hester, Mark E., Scharre, Douglas W., Santiskulvong, Chintda, Song, Sarah XueYing, Plummer, Jasmine T., Serrano, Geidy E., Beach, Thomas G., Duff, Karen E., Ma, Qin, and Fu, Hongjun

Published
2022
Full Text
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