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Functional dissection of Alzheimer’s disease brain gene expression signatures in humans and mouse models

Authors :
Xiaoyan Zhong
Ben Logsdon
Dawson
Jungwoo Wren Kim
Phillip
Tom V. Lee
Li-Huei Tsai
Hongkang Mei
Lara M. Mangravite
Levey Ai
Sarah M. Neuner
Paramita Chakrabarty
Gareth R. Howell
Ying-Wooi Wan
Wang M
Heidi Martini-Stoica
Carl Grant Mangleburg
Catherine C. Kaczorowski
Ping-Chieh Pao
Todd E. Golde
Hui Zheng
Ted M. Dawson
Zhandong Liu
Joshua M. Shulman
Yona Levites
Katherine Allison
Rami Al-Ouran
Jean-Vianney Haure-Mirande
Michelle E. Ehrlich
Publication Year :
2019
Publisher :
Cold Spring Harbor Laboratory, 2019.

Abstract

SUMMARYHuman brain transcriptomes can highlight biological pathways associated with Alzheimer’s disease (AD); however, challenges remain to link expression changes with causal triggers. We have examined 30 AD-associated, gene coexpression modules from human brains for overlap with 251 differentially-expressed gene sets from mouse brain RNA-sequencing experiments, including from models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus neurofibrillary tangle pathology and further reveal age- and sex-dependent expression signatures for AD progression. Human coexpression modules enriched for neuronal and/or microglial genes overlap broadly with signatures from mouse models of AD, Huntington’s disease, Amyotrophic Lateral Sclerosis, and also aging. Several human AD coexpression modules, including those implicated in the unfolded protein response and oxidative phosphorylation, were not activated in AD models, but instead were detected following other, unexpected mouse genetic manipulations. Our results comprise a powerful, cross-species resource and pinpoint experimental models for diverse features of AD pathophysiology from human brain transcriptomes.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....62e39d2626bb6400a1cd904b72b27815
Full Text :
https://doi.org/10.1101/506873