@article{2b976e47a05d48e2960408e328b96e4e,
title = "Human striatal glia differentially contribute to AD- and PD-specific neurodegeneration",
abstract = "The commonalities and differences in cell-type-specific pathways that lead to Alzheimer disease (AD) and Parkinson disease (PD) remain unknown. Here, we performed a single-nucleus transcriptome comparison of control, AD and PD striata. We describe three astrocyte subpopulations shared across different brain regions and evolutionarily conserved between humans and mice. We reveal common features between AD and PD astrocytes and regional differences that contribute toward amyloid pathology and neurodegeneration. In contrast, we found that transcriptomic changes in microglia are largely unique to each disorder. Our analysis identified a population of activated microglia that shared molecular signatures with murine disease-associated microglia (DAM) as well as disease-associated and regional differences in microglia transcriptomic changes linking microglia to disease-specific amyloid pathology, tauopathy and neuronal death. Finally, we delineate undescribed subpopulations of medium spiny neurons (MSNs) in the striatum and provide neuronal transcriptomic profiles suggesting disease-specific changes and selective neuronal vulnerability.",
author = "Jinbin Xu and Farsad, {Huifangjie L.} and Yiran Hou and Kia Barclay and Lopez, {Ben Anthony} and Shinnosuke Yamada and Saliu, {Ibrahim Olabayode} and Yiming Shi and Knight, {William C.} and Bateman, {Randall J.} and Benzinger, {Tammie L.S.} and Yi, {Jason J.} and Qingyun Li and Ting Wang and Perlmutter, {Joel S.} and Morris, {John C.} and Guoyan Zhao",
note = "Funding Information: We thank all participants and their families for their commitment and dedication to advancing research of diagnosis and treatment for AD and PD, and the Knight-ADRC and MDC research staff for their contributions. We thank N. Cairns, E.E. Franklin and M. Baxter of the Knight ADRC Neuropathology Core at Washington University School of Medicine (WUSM) for coordination of the tissue preparation and technical assistance. We thank the Genome Technology Access Center at the McDonnell Genome Institute at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant P30 CA91842 to the Siteman Cancer Center from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. We thank Brian Koebbe and Eric Martin from the High-Throughput Computing Facility at WUSM for providing high-throughput computational resources and support. The results published here are in whole or in part based on data obtained from the AD Knowledge Portal (https://adknowledgeportal.org). Samples for this study were provided by the Rush Alzheimer{\textquoteright}s Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by the NIA (grants P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984 and U01AG46152), the Illinois Department of Public Health and the Translational Genomics Research Institute. Finally, we thank the reviewers for their insightful suggestions that have enabled many of the discoveries reported in this manuscript. This work was supported by the GTAC@MGI Symposium Pilot Project Funding; the NIH/National Center for Advancing Translational Sciences (NCATS) grant UL1TR002345 to G.Z.; NIH grant 5T U24 HG012070 to T.W. and G.Z.; NIH grants R03AG070474, R21AG077643 and R01NS123571 in partial support of J.X. and G.Z.; NIH grants R01AG052550, R01AG054567 to T.L.S.B., research funded by NIH R01NS092865, R01AG054567, R01AG052550, U19AG032438 and P30AG06644 in support of H.L.F., W.C.K. and J.X.; by the Philip and Sima Needleman Student Fellowship in Regenerative Medicine in partial support of Y.H. and the Philippine Department of Science and Technology through the Philippine Council for Health Research and Development in partial support of B.A.L. This publication is solely the responsibility of the authors and does not necessarily represent the official view of the National Institute of Health. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript Funding Information: We thank all participants and their families for their commitment and dedication to advancing research of diagnosis and treatment for AD and PD, and the Knight-ADRC and MDC research staff for their contributions. We thank N. Cairns, E.E. Franklin and M. Baxter of the Knight ADRC Neuropathology Core at Washington University School of Medicine (WUSM) for coordination of the tissue preparation and technical assistance. We thank the Genome Technology Access Center at the McDonnell Genome Institute at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant P30 CA91842 to the Siteman Cancer Center from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. We thank Brian Koebbe and Eric Martin from the High-Throughput Computing Facility at WUSM for providing high-throughput computational resources and support. The results published here are in whole or in part based on data obtained from the AD Knowledge Portal ( https://adknowledgeportal.org ). Samples for this study were provided by the Rush Alzheimer{\textquoteright}s Disease Center, Rush University Medical Center, Chicago. Data collection was supported through funding by the NIA (grants P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984 and U01AG46152), the Illinois Department of Public Health and the Translational Genomics Research Institute. Finally, we thank the reviewers for their insightful suggestions that have enabled many of the discoveries reported in this manuscript. This work was supported by the GTAC@MGI Symposium Pilot Project Funding; the NIH/National Center for Advancing Translational Sciences (NCATS) grant UL1TR002345 to G.Z.; NIH grant 5T U24 HG012070 to T.W. and G.Z.; NIH grants R03AG070474, R21AG077643 and R01NS123571 in partial support of J.X. and G.Z.; NIH grants R01AG052550, R01AG054567 to T.L.S.B., research funded by NIH R01NS092865, R01AG054567, R01AG052550, U19AG032438 and P30AG06644 in support of H.L.F., W.C.K. and J.X.; by the Philip and Sima Needleman Student Fellowship in Regenerative Medicine in partial support of Y.H. and the Philippine Department of Science and Technology through the Philippine Council for Health Research and Development in partial support of B.A.L. This publication is solely the responsibility of the authors and does not necessarily represent the official view of the National Institute of Health. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2023",
month = mar,
doi = "10.1038/s43587-023-00363-8",
language = "English",
volume = "3",
pages = "346--365",
journal = "Nature Aging",
issn = "2662-8465",
number = "3",
}