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2. A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides.

Author

Paul, Kimberly C, Krolewski, Richard C, Lucumi Moreno, Edinson, Blank, Jack, Holton, Kristina M, Ahfeldt, Tim, Furlong, Melissa, Yu, Yu, Cockburn, Myles, Thompson, Laura K, Kreymerman, Alexander, Ricci-Blair, Elisabeth M, Li, Yu Jun, Patel, Heer B, Lee, Richard T, Bronstein, Jeff, Rubin, Lee L, Khurana, Vikram, and Ritz, Beate

Subjects
Humans, Parkinson Disease, Neurodegenerative Diseases, Pesticides, Induced Pluripotent Stem Cells, Dopaminergic Neurons, Neurosciences, Stem Cell Research - Induced Pluripotent Stem Cell, Prevention, Rural Health, Brain Disorders, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research, Parkinson's Disease, Neurodegenerative, Aging, Climate-Related Exposures and Conditions, Aetiology, 2.1 Biological and endogenous factors, Neurological
Abstract

Parkinson's disease (PD) is a complex neurodegenerative disease with etiology rooted in genetic vulnerability and environmental factors. Here we combine quantitative epidemiologic study of pesticide exposures and PD with toxicity screening in dopaminergic neurons derived from PD patient induced pluripotent stem cells (iPSCs) to identify Parkinson's-relevant pesticides. Agricultural records enable investigation of 288 specific pesticides and PD risk in a comprehensive, pesticide-wide association study. We associate long-term exposure to 53 pesticides with PD and identify co-exposure profiles. We then employ a live-cell imaging screening paradigm exposing dopaminergic neurons to 39 PD-associated pesticides. We find that 10 pesticides are directly toxic to these neurons. Further, we analyze pesticides typically used in combinations in cotton farming, demonstrating that co-exposures result in greater toxicity than any single pesticide. We find trifluralin is a driver of toxicity to dopaminergic neurons and leads to mitochondrial dysfunction. Our paradigm may prove useful to mechanistically dissect pesticide exposures implicated in PD risk and guide agricultural policy.

Published
2023

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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5. Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions

Author

Lam, Isabel, Ndayisaba, Alain, Lewis, Amanda J., Fu, YuHong, Sagredo, Giselle T., Kuzkina, Anastasia, Zaccagnini, Ludovica, Celikag, Meral, Sandoe, Jackson, Sanz, Ricardo L., Vahdatshoar, Aazam, Martin, Timothy D., Morshed, Nader, Ichihashi, Toru, Tripathi, Arati, Ramalingam, Nagendran, Oettgen-Suazo, Charlotte, Bartels, Theresa, Boussouf, Manel, Schäbinger, Max, Hallacli, Erinc, Jiang, Xin, Verma, Amrita, Tea, Challana, Wang, Zichen, Hakozaki, Hiroyuki, Yu, Xiao, Hyles, Kelly, Park, Chansaem, Wang, Xinyuan, Theunissen, Thorold W., Wang, Haoyi, Jaenisch, Rudolf, Lindquist, Susan, Stevens, Beth, Stefanova, Nadia, Wenning, Gregor, van de Berg, Wilma D.J., Luk, Kelvin C., Sanchez-Pernaute, Rosario, Gómez-Esteban, Juan Carlos, Felsky, Daniel, Kiyota, Yasujiro, Sahni, Nidhi, Yi, S. Stephen, Chung, Chee Yeun, Stahlberg, Henning, Ferrer, Isidro, Schöneberg, Johannes, Elledge, Stephen J., Dettmer, Ulf, Halliday, Glenda M., Bartels, Tim, and Khurana, Vikram

Published
2024
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6. Publisher Correction: A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides

Author

Paul, Kimberly C., Krolewski, Richard C., Lucumi Moreno, Edinson, Blank, Jack, Holton, Kristina M., Ahfeldt, Tim, Furlong, Melissa, Yu, Yu, Cockburn, Myles, Thompson, Laura K., Kreymerman, Alexander, Ricci-Blair, Elisabeth M., Li, Yu Jun, Patel, Heer B., Lee, Richard T., Bronstein, Jeff, Rubin, Lee L., Khurana, Vikram, and Ritz, Beate

Published
2023
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7. 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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8. Prevalence of RFC1-mediated spinocerebellar ataxia in a North American ataxia cohort.

Author

Aboud Syriani, Dona, Wong, Darice, Andani, Sameer, De Gusmao, Claudio, Mao, Yuanming, Sanyoura, May, Glotzer, Giacomo, Lockhart, Paul, Hassin-Baer, Sharon, Khurana, Vikram, Gomez, Christopher, Perlman, Susan, Das, Soma, and Fogel, Brent

Abstract

OBJECTIVE: We evaluated the prevalence of pathogenic repeat expansions in replication factor C subunit 1 (RFC1) and disabled adaptor protein 1 (DAB1) in an undiagnosed ataxia cohort from North America. METHODS: A cohort of 596 predominantly adult-onset patients with undiagnosed familial or sporadic cerebellar ataxia was evaluated at a tertiary referral ataxia center and excluded for common genetic causes of cerebellar ataxia. Patients were then screened for the presence of pathogenic repeat expansions in RFC1 (AAGGG) and DAB1 (ATTTC) using fluorescent repeat-primed PCR (RP-PCR). Two additional undiagnosed ataxia cohorts from different centers, totaling 302 and 13 patients, respectively, were subsequently screened for RFC1, resulting in a combined 911 subjects tested. RESULTS: In the initial cohort, 41 samples were identified with 1 expanded allele in the RFC1 gene (6.9%), and 9 had 2 expanded alleles (1.5%). For the additional cohorts, we found 20 heterozygous samples (6.6%) and 17 biallelic samples (5.6%) in the larger cohort and 1 heterozygous sample (7.7%) and 3 biallelic samples (23%) in the second. In total, 29 patients were identified with biallelic repeat expansions in RFC1 (3.2%). Of these 29 patients, 8 (28%) had a clinical diagnosis of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), 14 had cerebellar ataxia with neuropathy (48%), 4 had pure cerebellar ataxia (14%), and 3 had spinocerebellar ataxia (10%). No patients were identified with expansions in the DAB1 gene (spinocerebellar ataxia type 37). CONCLUSIONS: In a large undiagnosed ataxia cohort from North America, biallelic pathogenic repeat expansion in RFC1 was observed in 3.2%. Testing should be strongly considered in patients with ataxia, especially those with CANVAS or neuropathy.

Published
2020

9. Contributors

Author

Abdulai-Saiku, Samira, primary, Appel, Stanley H., additional, Arnold, Arthur P., additional, Arnold, Lisa M., additional, Arnold, Robert M., additional, Bacha, Alexa, additional, Backonja, Miroslav “Misha”, additional, Bailey, Zinzi D., additional, Bateman, Lucinda, additional, Beers, David R., additional, Berti, Anna, additional, Bhatnagar, Mamta, additional, Binder, Devin K., additional, Boido, Marina, additional, Boldrini, Maura, additional, Borsook, David, additional, Breakefield, Xandra O., additional, Brown, Robert H., additional, Burstein, Rami, additional, Butelman, Eduardo R., additional, Caplan, Louis R., additional, Chen, S., additional, Chesselet, Marie-Françoise, additional, Clemens, Stefan, additional, Clemens, Paula R., additional, Coyle, Joseph T., additional, DeWitt, John C., additional, Dubal, Dena B., additional, Dubljević, Veljko, additional, Feldman, Eva L., additional, Fischer, Beth A., additional, Flux, M.C., additional, Fortin, J.S., additional, Frasca, Angelisa, additional, Garbarini, Francesca, additional, Gasser, Thomas, additional, Gillespie, Charles F., additional, Gold, Michael S., additional, Gold, Stefan M., additional, Hagerman, Randi, additional, Hamel, Regan, additional, Haney, Craig, additional, Harris, James C., additional, Hassani, Sara, additional, Haughey, Norman J., additional, Heng, Vibol, additional, Horn, J., additional, Ionescu, Rosana-Bristena, additional, Iorio, Raffaele, additional, Irwin, David J., additional, Kaminski, Henry J., additional, Khammash, Dalia, additional, Khurana, Vikram, additional, Kilstrup-Nielsen, Charlotte, additional, Kim, Bhumsoo, additional, Kim, Boram, additional, Klein, Marieke, additional, Koen, Nastassja, additional, Konopaske, Glenn T., additional, Korecka, Joanna A., additional, Kornum, Birgitte Rahbek, additional, Kreek, Mary Jeanne, additional, Kristensson, Krister, additional, Krzak, Grzegorz, additional, Kusner, Linda L., additional, Landsberger, Nicoletta, additional, Lee, Edward B., additional, Li, Tong, additional, Liberski, Paweł P., additional, Lochner, Christine, additional, Lowry, Christopher A., additional, Mann, J. John, additional, Marincowitz, Clara, additional, Mayer, E.A., additional, Mayer, E.D., additional, McCall, Iris Coates, additional, McCullough, Louise D., additional, Meaney, Michael J., additional, Melo de Gusmao, Claudio, additional, Menesgere, Abhishek L., additional, Mignot, Emmanuel, additional, Mobley, William C., additional, Montalvo, Mayra, additional, Moreland-Capuia, Alisha R., additional, Neppi-Modona, Marco, additional, Nicaise, Alexandra M., additional, Nishi, Rae, additional, O'Toole, Orna, additional, Overk, Cassia, additional, Ozelius, Laurie, additional, Parsons, Matthew P., additional, Penticoff, H.B., additional, Peruzzotti-Jametti, Luca, additional, Peters, Owen M., additional, Peterson, Allison, additional, Phan, Jessica M., additional, Pittock, Sean J., additional, Pluchino, Stefano, additional, Polk, Thad A., additional, Puwanant, Araya, additional, Rajagopal, Shreya K., additional, Ravindranath, Vijayalakshmi, additional, Raymond, Lynn A., additional, Reed, Brian, additional, Ressler, Kerry J., additional, Ritchie, Diane L., additional, Rubin, Leah H., additional, Sakowski, Stacey A., additional, Saporta, Mario A., additional, Savonenko, Alena V., additional, Scharfman, Helen E., additional, Shapiro, Bruce K., additional, Sharma, Nutan, additional, Shaw, Cayce K., additional, Shy, Michael E., additional, Sikorska, Beata, additional, Silverman, Ethan J., additional, Simon, Roger P., additional, Simonyan, Kristina, additional, Sims-Robinson, Catrina, additional, Smeyne, Richard Jay, additional, Smith, Clay, additional, Smith, Colin, additional, Srinivasan, Sharan R., additional, Stein, Dan J., additional, Stephen, Christopher D., additional, Subramanian, Indu, additional, Szabo, Edina, additional, Thomas, Alissa A., additional, Tovar-y-Romo, Luis B., additional, Vahabzadeh, Arshya, additional, Vercelli, Alessandro, additional, Viera-Ortiz, Ashley, additional, Wallin, Mitchell T., additional, Werling, Donna M., additional, Wichmann, Thomas, additional, Wiley, Clayton A., additional, Williams, David R., additional, Willis, Cory, additional, Wong, Philip C., additional, Yuferov, Vadim, additional, Zhao, Weihua, additional, Zigmond, Michael J., additional, and Živković, Saša A., additional

Published
2023
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10. Repeat expansion disorders

Author

Srinivasan, Sharan R., primary, Melo de Gusmao, Claudio, additional, Korecka, Joanna A., additional, and Khurana, Vikram, additional

Published
2023
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13. Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting

Author

Walsh, Ryan R, Krismer, Florian, Galpern, Wendy R, Wenning, Gregor K, Low, Phillip A, Halliday, Glenda, Koroshetz, Walter J, Holton, Janice, Quinn, Niall P, Rascol, Olivier, Shaw, Leslie M, Eidelberg, David, Bower, Pam, Cummings, Jeffrey L, Abler, Victor, Biedenharn, Judy, Bitan, Gal, Brooks, David J, Brundin, Patrik, Fernandez, Hubert, Fortier, Philip, Freeman, Roy, Gasser, Thomas, Hewitt, Art, Höglinger, Günter U, Huentelman, Matt J, Jensen, Poul H, Jeromin, Andreas, Kang, Un Jung, Kaufmann, Horacio, Kellerman, Lawrence, Khurana, Vikram, Klockgether, Thomas, Kim, Woojin Scott, Langer, Carol, LeWitt, Peter, Masliah, Eliezer, Meissner, Wassilios, Melki, Ronald, Ostrowitzki, Susanne, Piantadosi, Steven, Poewe, Werner, Robertson, David, Roemer, Cyndi, Schenk, Dale, Schlossmacher, Michael, Schmahmann, Jeremy D, Seppi, Klaus, Shih, Lily, Siderowf, Andrew, Stebbins, Glenn T, Stefanova, Nadia, Tsuji, Shoji, Sutton, Sharon, and Zhang, Jing

Subjects
Rare Diseases, Humans, Multiple System Atrophy, Nevada, Patient Advocacy, Research Design, Clinical Sciences, Neurosciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Multiple system atrophy (MSA) is a rare neurodegenerative disorder with substantial knowledge gaps despite recent gains in basic and clinical research. In order to make further advances, concerted international collaboration is vital. In 2014, an international meeting involving leaders in the field and MSA advocacy groups was convened in Las Vegas, Nevada, to identify critical research areas where consensus and progress was needed to improve understanding, diagnosis, and treatment of the disease. Eight topic areas were defined: pathogenesis, preclinical modeling, target identification, endophenotyping, clinical measures, imaging biomarkers, nonimaging biomarkers, treatments/trial designs, and patient advocacy. For each topic area, an expert served as a working group chair and each working group developed priority-ranked research recommendations with associated timelines and pathways to reach the intended goals. In this report, each groups' recommendations are provided.

Published
2018

14. 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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15. 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

16. Toward the quantification of α-synuclein aggregates with digital seed amplification assays

Author

Gilboa, Tal, primary, Swank, Zoe, additional, Thakur, Rohan, additional, Gould, Russell A., additional, Ooi, Kean Hean, additional, Norman, Maia, additional, Flynn, Elizabeth A., additional, Deveney, Brendan T., additional, Chen, Anqi, additional, Borberg, Ella, additional, Kuzkina, Anastasia, additional, Ndayisaba, Alain, additional, Khurana, Vikram, additional, Weitz, David A., additional, and Walt, David R., additional

Published
2024
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17. Health phenome of Parkinson’s patients reveals prominent mood-sleep cluster

Author

Olsen, Abby, primary, Locascio, Joseph, additional, Tuncali, Idil, additional, Laroussi, Nada, additional, Abatzis, Elena, additional, Kamenskaya, Polina, additional, Kuras, Yuliya, additional, Yi, Tom, additional, Videnovic, Aleks, additional, Hayes, Michael, additional, Ho, Gary, additional, Paulson, Jordan, additional, Khurana, Vikram, additional, Herrington, Todd, additional, Hyman, Bradley, additional, Selkoe, Dennis, additional, Growdon, John, additional, Gomperts, Stephen, additional, Riise, Trond, additional, Schwarzschild, Michael, additional, Hung, Albert, additional, Wills, Anne, additional, and Scherzer, Clemens, additional

Published
2023
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22. 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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24. Rapid iPSC inclusionopathy models shed light on formation, consequence and molecular subtype of α-synuclein inclusions

Author

Lam, Isabel, primary, Ndayisaba, Alain, additional, Lewis, Amanda J., additional, Fu, YuHong, additional, Sagredo, Giselle T., additional, Zaccagnini, Ludovica, additional, Sandoe, Jackson, additional, Sanz, Ricardo L., additional, Vahdatshoar, Aazam, additional, Martin, Timothy D., additional, Morshed, Nader, additional, Ichihashi, Toru, additional, Tripathi, Arati, additional, Ramalingam, Nagendran, additional, Oettgen-Suazo, Charlotte, additional, Bartels, Theresa, additional, Schäbinger, Max, additional, Hallacli, Erinc, additional, Jiang, Xin, additional, Verma, Amrita, additional, Tea, Challana, additional, Wang, Zichen, additional, Hakozaki, Hiroyuki, additional, Yu, Xiao, additional, Hyles, Kelly, additional, Park, Chansaem, additional, Theunissen, Thorold W., additional, Wang, Haoyi, additional, Jaenisch, Rudolf, additional, Lindquist, Susan, additional, Stevens, Beth, additional, Stefanova, Nadia, additional, Wenning, Gregor, additional, Luk, Kelvin C., additional, Pernaute, Rosario Sanchez, additional, Gómez-Esteban, Juan Carlos, additional, Felsky, Daniel, additional, Kiyota, Yasujiro, additional, Sahni, Nidhi, additional, Yi, S. Stephen, additional, Chung, Chee-Yeun, additional, Stahlberg, Henning, additional, Ferrer, Isidro, additional, Schöneberg, Johannes, additional, Elledge, Stephen J., additional, Dettmer, Ulf, additional, Halliday, Glenda M., additional, Bartels, Tim, additional, and Khurana, Vikram, additional

Published
2022
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25. 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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26. Toward More Accessible Fully Automated 3D Volumetric MRI Decision Trees for the Differential Diagnosis of Multiple System Atrophy, Related Disorders, and Age-Matched Healthy Subjects

Author

Kim, Jisoo, primary, Young, Geoffrey S., additional, Willett, Andrew S., additional, Pitaro, Ariana T., additional, Crotty, Grace F., additional, Mesidor, Merlyne, additional, Jones, Kristie A., additional, Bay, Camden, additional, Zhang, Min, additional, Feany, Mel B., additional, Xu, Xiaoyin, additional, Qin, Lei, additional, and Khurana, Vikram, additional

Published
2022
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27. The Parkinson’s disease protein alpha-synuclein is a modulator of processing bodies and mRNA stability

Author

Hallacli, Erinc, primary, Kayatekin, Can, additional, Nazeen, Sumaiya, additional, Wang, Xiou H., additional, Sheinkopf, Zoe, additional, Sathyakumar, Shubhangi, additional, Sarkar, Souvarish, additional, Jiang, Xin, additional, Dong, Xianjun, additional, Di Maio, Roberto, additional, Wang, Wen, additional, Keeney, Matthew T., additional, Felsky, Daniel, additional, Sandoe, Jackson, additional, Vahdatshoar, Aazam, additional, Udeshi, Namrata D., additional, Mani, D.R., additional, Carr, Steven A., additional, Lindquist, Susan, additional, De Jager, Philip L., additional, Bartel, David P., additional, Myers, Chad L., additional, Greenamyre, J. Timothy, additional, Feany, Mel B., additional, Sunyaev, Shamil R., additional, Chung, Chee Yeun, additional, and Khurana, Vikram, additional

Published
2022
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29. Identification and Rescue of α-Synuclein Toxicity in Parkinson Patient-Derived Neurons

Author

Chung, Chee Yeun, Khurana, Vikram, Auluck, Pavan K., Tardiff, Daniel F., Mazzulli, Joseph R., Söldner, Frank, Baru, Valeriya, Lou, Yali, Freyzon, Yelena, Cho, Sukhee, Mungenast, Alison E., Muffat, Julien, Mitalipova, Maisam, Pluth, Michael D., Jui, Nathan T., Schüle, Birgitt, Lippard, Stephen J., Tsai, Li-Huei, Krainc, Dimitri, Buchwald, Stephen L., Jaenisch, Rudolf, and Lindquist, Susan

Published
2013
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30. Coupling comprehensive pesticide-wide association study to iPSC dopaminergic screening identifies and classifies Parkinson-relevant pesticides

Author

Paul, Kimberly C, primary, Krolewski, Richard C, additional, Moreno, Edinson Lucumi, additional, Blank, Jack, additional, Holton, Kris, additional, Ahfeldt, Tim, additional, Furlong, Melissa, additional, Yu, Yu, additional, Cockburn, Myles, additional, Thompson, Laura K, additional, Bronstein, Jeff, additional, Rubin, Lee L., additional, Khurana, Vikram, additional, and Ritz, Beate, additional

Published
2022
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31. Towards a phenome-wide view of Parkinson’s disease

Author

Olsen, Abby L., primary, Locascio, Joseph J., additional, Tuncali, Idil, additional, Laroussi, Nada, additional, Abatzis, Elena, additional, Kamenskaya, Polina, additional, Kuras, Yuliya, additional, Yi, Tom, additional, Videnovic, Aleksandar, additional, Hayes, Michael T., additional, Ho, Gary P. H., additional, Paulson, Jordan, additional, Khurana, Vikram, additional, Herrington, Todd M., additional, Hyman, Bradley T., additional, Selkoe, Dennis J., additional, Growdon, John H., additional, Gomperts, Stephen N., additional, Riise, Trond, additional, Schwarzschild, Michael A., additional, Hung, Albert Y., additional, Wills, Anne-Marie, additional, and Scherzer, Clemens R., additional

Published
2022
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37. Identification and Rescue of a-Synuclein Toxicity in Parkinson Patient-Derived Neurons

Author

Chung, Chee Yeun, Khurana, Vikram, Auluck, Pavan K., Tardiff, Daniel F., Mazzulli, Joseph R., Soldner, Frank, Baru, Valeriya, Lou, Yali, Freyzon, Yelena, Cho, Sukhee, Mungenast, Alison E., Muffat, Julien, Mitalipova, Maisam, Pluth, Michael D., Jui, Nathan T., Schüle, Birgitt, Lippard, Stephen J., Tsai, Li-Huei, Krainc, Dimitri, Buchwald, Stephen L., Jaenisch, Rudolf, and Lindquist, Susan

Published
2013
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39. Prevalence of RFC1-Mediated Spinocerebellar Ataxia in a United States Ataxia Cohort (1989)

Author

Syriani, Dona Aboud, primary, Wong, Darice, additional, De Gusmao, Claudio, additional, Andani, Sameer, additional, Mao, Yuanming, additional, Glotzer, Giacomo, additional, Lockhart, Paul, additional, Hassin-Baer, Sharon, additional, Khurana, Vikram, additional, Das, Soma, additional, Gomez, Christopher, additional, Perlman, Susan, additional, and Fogel, Brent, additional

Published
2020
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40. Prevalence of RFC1-Mediated Spinocerebellar Ataxia in a United States Ataxia Cohort

Author

Syriani, Dona Aboud, primary, Wong, Darice, additional, De Gusmao, Claudio M., additional, Andani, Sameer, additional, Mao, Yuanming, additional, Glotzer, Giacomo, additional, Lockhart, Paul J., additional, Hassin-Baer, Sharon, additional, Khurana, Vikram, additional, Das, Soma, additional, Gomez, Christopher M., additional, Perlman, Susan, additional, and Fogel, Brent L., additional

Published
2019
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42. Inhibiting Stearoyl-CoA Desaturase Ameliorates α-Synuclein Cytotoxicity

Author

Vincent, Benjamin M., primary, Tardiff, Daniel F., additional, Piotrowski, Jeff S., additional, Aron, Rebecca, additional, Lucas, Matthew C., additional, Chung, Chee Yeun, additional, Bacherman, Helene, additional, Chen, YiQun, additional, Pires, Michelle, additional, Subramaniam, Radha, additional, Doshi, Dimple B., additional, Sadlish, Heather, additional, Raja, Waseem K., additional, Solís, Eric J., additional, Khurana, Vikram, additional, Le Bourdonnec, Bertrand, additional, Scannevin, Robert H., additional, and Rhodes, Kenneth J., additional

Published
2018
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43. Prediction of cognition in Parkinson's disease with a clinical–genetic score: a longitudinal analysis of nine cohorts

Author

Liu, Ganqiang, Locascio, Joseph J, Winder-Rhodes, Sophie, Vidailhet, Marie, Bonnet, Anne-Marie, Bonnet, Cecilia, Corvol, Jean-Christophe, Elbaz, Alexis, Grabli, David, Hartmann, Andreas, Klebe, Stephan, Lacomblez, Lucette, Mangone, Graziella, Tanner, Caroline M, Bourdain, Frédéric, Brandel, Jean-Philippe, Derkinderen, Pascal, Durif, Franck, Mesnage, Valérie, Pico, Fernando, Rascol, Olivier, Brefel-Courbon, Christine, Ory-Magne, Fabienne, Lang, Anthony E, Forlani, Sylvie, Lesage, Suzanne, Tahiri, Khadija, Albin, Roger, Alcalay, Roy, Ascherio, Alberto, Bowman, Dubois, Chen-Plotkin, Alice, Dawson, Ted, Eberly, Shirley, Dewey, Richard, German, Dwight, Saunders-Pullman, Rachel, Scherzer, Clemens, Vaillancourt, David, Petyuk, Vladislav, West, Andy, Zhang, Jing, Brice, Alexis, Ravina, Bernard, Shoulson, Ira, Cormier-Dequaire, Florence, Heutink, Peter, van Hilten, Jacobus J, Barker, Roger A, Williams-Gray, Caroline H, Marinus, Johan, Scherzer, Clemens R, HBS, CamPaIGN, PICNICS, PROPARK, Boot, Brendon, PSG, DIGPD, PDBP, Hyman, Bradley T, Ivinson, Adrian J, Trisini-Lipsanopoulos, Ana, Franco, Daly, Burke, Kyle, Sudarsky, Lewis R, Liao, Zhixiang, 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, Page, Kara, 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, Li, Haining, Stalberg, Gabriel, Jansen, Iris E, Barker, Roger, Foltynie, Tom, Williams-Gray, Caroline, Robbins, Trevor, Brayne, Carol, Mason, Sarah, Breen, David P, Cummins, Gemma, Evans, Jonathan, Mallet, Alain, Neurology, Amsterdam Neuroscience - Neurodegeneration, and Human genetics

Subjects
0301 basic medicine, Gerontology, Male, medicine.medical_specialty, Population, etiology [Cognitive Dysfunction], 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Dementia, Humans, Cognitive Dysfunction, ddc:610, Longitudinal Studies, Cognitive decline, education, Aged, Proportional Hazards Models, Aged, 80 and over, education.field_of_study, Mini–Mental State Examination, Framingham Risk Score, medicine.diagnostic_test, Proportional hazards model, Hazard ratio, Parkinson Disease, Middle Aged, medicine.disease, Prognosis, diagnosis [Dementia], 030104 developmental biology, diagnosis [Cognitive Dysfunction], Quartile, Disease Progression, Female, Neurology (clinical), etiology [Dementia], complications [Parkinson Disease], Psychology, diagnosis [Parkinson Disease], 030217 neurology & neurosurgery, Algorithms
Abstract

Summary Background Cognitive decline is a debilitating manifestation of disease progression in Parkinson's disease. We aimed to develop a clinical–genetic score to predict global cognitive impairment in patients with the disease. Methods In this longitudinal analysis, we built a prediction algorithm for global cognitive impairment (defined as Mini Mental State Examination [MMSE] ≤25) using data from nine cohorts of patients with Parkinson's disease from North America and Europe assessed between 1986 and 2016. Candidate predictors of cognitive decline were selected through a backward eliminated Cox's proportional hazards analysis using the Akaike's information criterion. These were used to compute the multivariable predictor on the basis of data from six cohorts included in a discovery population. Independent replication was attained in patients from a further three independent longitudinal cohorts. The predictive score was rebuilt and retested in 10 000 training and test sets randomly generated from the entire study population. Findings 3200 patients with Parkinson's disease who were longitudinally assessed with 27 022 study visits between 1986 and 2016 in nine cohorts from North America and Europe were assessed for eligibility. 235 patients with MMSE ≤25 at baseline and 135 whose first study visit occurred more than 12 years from disease onset were excluded. The discovery population comprised 1350 patients (after further exclusion of 334 with missing covariates) from six longitudinal cohorts with 5165 longitudinal visits over 12·8 years (median 2·8, IQR 1·6–4·6). Age at onset, baseline MMSE, years of education, motor exam score, sex, depression, and β-glucocerebrosidase ( GBA ) mutation status were included in the prediction model. The replication population comprised 1132 patients (further excluding 14 patients with missing covariates) from three longitudinal cohorts with 19 127 follow-up visits over 8·6 years (median 6·5, IQR 4·1–7·2). The cognitive risk score predicted cognitive impairment within 10 years of disease onset with an area under the curve (AUC) of more than 0·85 in both the discovery (95% CI 0·82–0·90) and replication (95% CI 0·78–0·91) populations. Patients scoring in the highest quartile for cognitive risk score had an increased hazard for global cognitive impairment compared with those in the lowest quartile (hazard ratio 18·4 [95% CI 9·4–36·1]). Dementia or disabling cognitive impairment was predicted with an AUC of 0·88 (95% CI 0·79–0·94) and a negative predictive value of 0·92 (95% 0·88–0·95) at the predefined cutoff of 0·196. Performance was stable in 10 000 randomly resampled subsets. Interpretation Our predictive algorithm provides a potential test for future cognitive health or impairment in patients with Parkinson's disease. This model could improve trials of cognitive interventions and inform on prognosis. Funding National Institutes of Health, US Department of Defense.

Published
2017

44. Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting

Author

Walsh, Ryan R., primary, Krismer, Florian, additional, Galpern, Wendy R., additional, Wenning, Gregor K., additional, Low, Phillip A., additional, Halliday, Glenda, additional, Koroshetz, Walter J., additional, Holton, Janice, additional, Quinn, Niall P., additional, Rascol, Olivier, additional, Shaw, Leslie M., additional, Eidelberg, David, additional, Bower, Pam, additional, Cummings, Jeffrey L., additional, Abler, Victor, additional, Biedenharn, Judy, additional, Bitan, Gal, additional, Brooks, David J., additional, Brundin, Patrik, additional, Fernandez, Hubert, additional, Fortier, Philip, additional, Freeman, Roy, additional, Gasser, Thomas, additional, Hewitt, Art, additional, Höglinger, Günter U., additional, Huentelman, Matt J., additional, Jensen, Poul H., additional, Jeromin, Andreas, additional, Kang, Un Jung, additional, Kaufmann, Horacio, additional, Kellerman, Lawrence, additional, Khurana, Vikram, additional, Klockgether, Thomas, additional, Kim, Woojin Scott, additional, Langer, Carol, additional, LeWitt, Peter, additional, Masliah, Eliezer, additional, Meissner, Wassilios, additional, Melki, Ronald, additional, Ostrowitzki, Susanne, additional, Piantadosi, Steven, additional, Poewe, Werner, additional, Robertson, David, additional, Roemer, Cyndi, additional, Schenk, Dale, additional, Schlossmacher, Michael, additional, Schmahmann, Jeremy D., additional, Seppi, Klaus, additional, Shih, Lily, additional, Siderowf, Andrew, additional, Stebbins, Glenn T., additional, Stefanova, Nadia, additional, Tsuji, Shoji, additional, Sutton, Sharon, additional, and Zhang, Jing, additional

Published
2017
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46. PROTEOME-SCALE MOLECULAR NETWORKS MECHANISTICALLY LINK ALPHA-SYNUCLEIN TO DIVERSE GENETIC RISK FACTORS FOR PARKINSONISM (P1.004)

Author

Khurana, Vikram, primary, Peng, Jian, additional, Chung, Chee Yeun, additional, Fanning, Saranna, additional, Tardiff, Daniel, additional, Bartels, Theresa, additional, Yi, Song, additional, Sahni, Nidhi, additional, Loh, Ken, additional, Costanzo, Michael, additional, Luis, Bryan San, additional, Schondorf, David, additional, Deleidi, Michela, additional, Boone, Charles, additional, Fraenkel, Ernest, additional, Hill, David, additional, Vidal, Marc, additional, Berger, Bonnie, additional, and Lindquist, Susan, additional

Published
2017
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47. Genome-Scale Networks Link Neurodegenerative Disease Genes to α-Synuclein through Specific Molecular Pathways

Author

Khurana, Vikram, primary, Peng, Jian, additional, Chung, Chee Yeun, additional, Auluck, Pavan K., additional, Fanning, Saranna, additional, Tardiff, Daniel F., additional, Bartels, Theresa, additional, Koeva, Martina, additional, Eichhorn, Stephen W., additional, Benyamini, Hadar, additional, Lou, Yali, additional, Nutter-Upham, Andy, additional, Baru, Valeriya, additional, Freyzon, Yelena, additional, Tuncbag, Nurcan, additional, Costanzo, Michael, additional, San Luis, Bryan-Joseph, additional, Schöndorf, David C., additional, Barrasa, M. Inmaculada, additional, Ehsani, Sepehr, additional, Sanjana, Neville, additional, Zhong, Quan, additional, Gasser, Thomas, additional, Bartel, David P., additional, Vidal, Marc, additional, Deleidi, Michela, additional, Boone, Charles, additional, Fraenkel, Ernest, additional, Berger, Bonnie, additional, and Lindquist, Susan, additional

Published
2017
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48. In Situ Peroxidase Labeling and Mass-Spectrometry Connects Alpha-Synuclein Directly to Endocytic Trafficking and mRNA Metabolism in Neurons

Author

Chung, Chee Yeun, primary, Khurana, Vikram, additional, Yi, Song, additional, Sahni, Nidhi, additional, Loh, Ken H., additional, Auluck, Pavan K., additional, Baru, Valeriya, additional, Udeshi, Namrata D., additional, Freyzon, Yelena, additional, Carr, Steven A., additional, Hill, David E., additional, Vidal, Marc, additional, Ting, Alice Y., additional, and Lindquist, Susan, additional

Published
2017
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