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Meta-Analysis of the Alzheimer’s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models

dc.contributor.authorWan, Ying-Wooi
dc.contributor.authorAl-Ouran, Rami
dc.contributor.authorMangleburg, Carl G.
dc.contributor.authorPerumal, Thanneer M.
dc.contributor.authorLee, Tom V.
dc.contributor.authorAllison, Katherine
dc.contributor.authorSwarup, Vivek
dc.contributor.authorFunk, Cory C.
dc.contributor.authorGaiteri, Chris
dc.contributor.authorAllen, Mariet
dc.contributor.authorWang, Minghui
dc.contributor.authorNeuner, Sarah M.
dc.contributor.authorKaczorowski, Catherine C.
dc.contributor.authorPhilip, Vivek M.
dc.contributor.authorHowell, Gareth R.
dc.contributor.authorMartini-Stoica, Heidi
dc.contributor.authorZheng, Hui
dc.contributor.authorMei, Hongkang
dc.contributor.authorZhong, Xiaoyan
dc.contributor.authorKim, Jungwoo Wren
dc.contributor.authorDawson, Valina L.
dc.contributor.authorDawson, Ted M.
dc.contributor.authorPao, Ping-Chieh
dc.contributor.authorTsai, Li-Huei
dc.contributor.authorHaure-Mirande, Jean-Vianney
dc.contributor.authorEhrlich, Michelle E.
dc.contributor.authorChakrabarty, Paramita
dc.contributor.authorLevites, Yona
dc.contributor.authorWang, Xue
dc.contributor.authorDammer, Eric B.
dc.contributor.authorSrivastava, Gyan
dc.contributor.authorMukherjee, Sumit
dc.contributor.authorSieberts, Solveig K.
dc.contributor.authorOmberg, Larsson
dc.contributor.authorDang, Kristen D.
dc.contributor.authorEddy, James A.
dc.contributor.authorSnyder, Phil
dc.contributor.authorChae, Yooree
dc.contributor.authorAmberkar, Sandeep
dc.contributor.authorWei, Wenbin
dc.contributor.authorHide, Winston
dc.contributor.authorPreuss, Christoph
dc.contributor.authorErgun, Ayla
dc.contributor.authorEbert, Phillip J.
dc.contributor.authorAirey, David C.
dc.contributor.authorMostafavi, Sara
dc.contributor.authorYu, Lei
dc.contributor.authorKlein, Hans-Ulrich
dc.contributor.authorCarter, Gregory W.
dc.contributor.authorCollier, David A.
dc.contributor.authorGolde, Todd E.
dc.contributor.authorLevey, Allan I.
dc.contributor.authorBennett, David A.
dc.contributor.authorEstrada, Karol
dc.contributor.authorTownsend, T. Matthew
dc.contributor.authorZhang, Bin
dc.contributor.authorSchadt, Eric
dc.contributor.authorDe Jager, Philip L.
dc.contributor.authorPrice, Nathan D.
dc.contributor.authorErtekin-Taner, Nilüfer
dc.contributor.authorLiu, Zhandong
dc.contributor.authorShulman, Joshua M.
dc.contributor.authorMangravite, Lara M.
dc.contributor.authorLogsdon, Benjamin A.
dc.date.accessioned2022-03-14T18:10:13Z
dc.date.available2021-10-27T20:30:14Z
dc.date.available2022-03-14T18:10:13Z
dc.date.issued2020-07
dc.date.submitted2020-06
dc.identifier.issn2211-1247
dc.identifier.urihttps://hdl.handle.net/1721.1/135985.2
dc.description.abstract© 2020 The Authors We present a consensus atlas of the human brain transcriptome in Alzheimer's disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington's disease, amyotrophic lateral sclerosis, and aging. Other human coexpression modules, including those implicated in proteostasis, are not activated in AD models but rather following other, unexpected genetic manipulations. Our results comprise a cross-species resource, highlighting transcriptional networks altered by human brain pathophysiology and identifying correspondences with mouse models for AD preclinical studies.en_US
dc.language.isoen
dc.publisherElsevier BVen_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.celrep.2020.107908en_US
dc.rightsCreative Commons Attribution 4.0 International licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.sourceElsevieren_US
dc.titleMeta-Analysis of the Alzheimer’s Disease Human Brain Transcriptome and Functional Dissection in Mouse Modelsen_US
dc.typeArticleen_US
dc.contributor.departmentPicower Institute for Learning and Memory
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciences
dc.relation.journalCell Reportsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2021-03-22T18:43:49Z
dspace.orderedauthorsWan, Y-W; Al-Ouran, R; Mangleburg, CG; Perumal, TM; Lee, TV; Allison, K; Swarup, V; Funk, CC; Gaiteri, C; Allen, M; Wang, M; Neuner, SM; Kaczorowski, CC; Philip, VM; Howell, GR; Martini-Stoica, H; Zheng, H; Mei, H; Zhong, X; Kim, JW; Dawson, VL; Dawson, TM; Pao, P-C; Tsai, L-H; Haure-Mirande, J-V; Ehrlich, ME; Chakrabarty, P; Levites, Y; Wang, X; Dammer, EB; Srivastava, G; Mukherjee, S; Sieberts, SK; Omberg, L; Dang, KD; Eddy, JA; Snyder, P; Chae, Y; Amberkar, S; Wei, W; Hide, W; Preuss, C; Ergun, A; Ebert, PJ; Airey, DC; Mostafavi, S; Yu, L; Klein, H-U; Carter, GW; Collier, DA; Golde, TE; Levey, AI; Bennett, DA; Estrada, K; Townsend, TM; Zhang, B; Schadt, E; De Jager, PL; Price, ND; Ertekin-Taner, N; Liu, Z; Shulman, JM; Mangravite, LM; Logsdon, BAen_US
dspace.date.submission2021-03-22T18:43:56Z
mit.journal.volume32en_US
mit.journal.issue2en_US
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work Neededen_US


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