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

Wan, Ying-Wooi; Al-Ouran, Rami; Mangleburg, Carl G.; Perumal, Thanneer M.; Lee, Tom V.; Allison, Katherine; Swarup, Vivek; Funk, Cory C.; Gaiteri, Chris; Allen, Mariet; Wang, Minghui; Neuner, Sarah M.; Kaczorowski, Catherine C.; Philip, Vivek M.; Howell, Gareth R.; Martini-Stoica, Heidi; Zheng, Hui; Mei, Hongkang; Zhong, Xiaoyan; Kim, Jungwoo Wren; Dawson, Valina L.; Dawson, Ted M.; Pao, Ping-Chieh; Tsai, Li-Huei; Haure-Mirande, Jean-Vianney; Ehrlich, Michelle E.; Chakrabarty, Paramita; Levites, Yona; Wang, Xue; Dammer, Eric B.; Srivastava, Gyan; Mukherjee, Sumit; Sieberts, Solveig K.; Omberg, Larsson; Dang, Kristen D.; Eddy, James A.; Snyder, Phil; Chae, Yooree; Amberkar, Sandeep; Wei, Wenbin; Hide, Winston; Preuss, Christoph; Ergun, Ayla; Ebert, Phillip J.; Airey, David C.; Mostafavi, Sara; Yu, Lei; Klein, Hans-Ulrich; Carter, Gregory W.; Collier, David A.; Golde, Todd E.; Levey, Allan I.; Bennett, David A.; Estrada, Karol; Townsend, T. Matthew; Zhang, Bin; Schadt, Eric; De Jager, Philip L.; Price, Nathan D.; Ertekin-Taner, Nilüfer; Liu, Zhandong; Shulman, Joshua M.; Mangravite, Lara M.; Logsdon, Benjamin A.

doi:10.1016/j.celrep.2020.107908

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

Wan, Ying-Wooi; Al-Ouran, Rami; Mangleburg, Carl G.; Perumal, Thanneer M.; Lee, Tom V.; Allison, Katherine; Swarup, Vivek; Funk, Cory C.; Gaiteri, Chris; Allen, Mariet; Wang, Minghui; Neuner, Sarah M.; Kaczorowski, Catherine C.; Philip, Vivek M.; Howell, Gareth R.; Martini-Stoica, Heidi; Zheng, Hui; Mei, Hongkang; Zhong, Xiaoyan; Kim, Jungwoo Wren; Dawson, Valina L.; Dawson, Ted M.; Pao, Ping-Chieh; Tsai, Li-Huei; Haure-Mirande, Jean-Vianney; Ehrlich, Michelle E.; Chakrabarty, Paramita; Levites, Yona; Wang, Xue; Dammer, Eric B.; Srivastava, Gyan; Mukherjee, Sumit; Sieberts, Solveig K.; Omberg, Larsson; Dang, Kristen D.; Eddy, James A.; Snyder, Phil; Chae, Yooree; Amberkar, Sandeep; Wei, Wenbin; Hide, Winston; Preuss, Christoph; Ergun, Ayla; Ebert, Phillip J.; Airey, David C.; Mostafavi, Sara; Yu, Lei; Klein, Hans-Ulrich; Carter, Gregory W.; Collier, David A.; Golde, Todd E.; Levey, Allan I.; Bennett, David A.; Estrada, Karol; Townsend, T. Matthew; Zhang, Bin; Schadt, Eric; De Jager, Ph...

Authors

Ying-Wooi Wan

Rami Al-Ouran

Carl G. Mangleburg

Thanneer M. Perumal

Tom V. Lee

Katherine Allison

Vivek Swarup

Cory C. Funk

Chris Gaiteri

Mariet Allen

Minghui Wang

Sarah M. Neuner

Catherine C. Kaczorowski

Vivek M. Philip

Gareth R. Howell

Heidi Martini-Stoica

Hui Zheng

Hongkang Mei

Xiaoyan Zhong

Jungwoo Wren Kim

Valina L. Dawson

Ted M. Dawson

Ping-Chieh Pao

Li-Huei Tsai

Jean-Vianney Haure-Mirande

Michelle E. Ehrlich

Paramita Chakrabarty

Yona Levites

Xue Wang

Eric B. Dammer

Gyan Srivastava

Sumit Mukherjee

Solveig K. Sieberts

Larsson Omberg

Kristen D. Dang

James A. Eddy

Phil Snyder

Yooree Chae

Sandeep Amberkar

Dr Wenbin Wei wenbin.wei2@durham.ac.uk
Chief Experimental Officer (Bioinformatics)

Winston Hide

Christoph Preuss

Ayla Ergun

Phillip J. Ebert

David C. Airey

Sara Mostafavi

Lei Yu

Hans-Ulrich Klein

Gregory W. Carter

David A. Collier

Todd E. Golde

Allan I. Levey

David A. Bennett

Karol Estrada

T. Matthew Townsend

Bin Zhang

Eric Schadt

Philip L. De Jager

Nathan D. Price

Nilüfer Ertekin-Taner

Zhandong Liu

Joshua M. Shulman

Lara M. Mangravite

Benjamin A. Logsdon

Abstract

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.

Citation

Wan, Y., Al-Ouran, R., Mangleburg, C. G., Perumal, T. M., Lee, T. V., Allison, K., …Logsdon, B. A. (2020). Meta-Analysis of the Alzheimer’s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models. Cell Reports, 32(2), Article 107908. https://doi.org/10.1016/j.celrep.2020.107908

Journal Article Type	Article
Acceptance Date	Jun 24, 2020
Online Publication Date	Jul 14, 2020
Publication Date	2020-07
Deposit Date	Jul 22, 2020
Publicly Available Date	Jul 22, 2020
Journal	Cell Reports
Print ISSN	2211-1247
Publisher	Cell Press
Peer Reviewed	Peer Reviewed
Volume	32
Issue	2
Article Number	107908
DOI	https://doi.org/10.1016/j.celrep.2020.107908