Cell reports · 2020

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

СтатьяМетаанализПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен

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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, Accelerating Medicines Partnership-Alzheimer’s Disease Consortium, 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

Аннотация

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.

Предметные рубрики MeSH

Alzheimer Disease Animals Brain Case-Control Studies Disease Models, Animal Female Gene Expression Profiling Gene Expression Regulation Gene Regulatory Networks Humans Male Mice Sex Characteristics Species Specificity Transcription, Genetic Transcriptome

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

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH