Journal
CELL REPORTS
Volume 32, Issue 2, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.107908
Keywords
-
Categories
Funding
- National Institute on Aging (NIA) grants [P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984, U01AG46152, P50 AG016574, R01 AG032990]
- Illinois Department of Public Health [U01 AG046139, R01 AG018023, U01 AG006576, U01 AG006786, R01 AG025711, R01 AG017216, R01 AG003949, P30 AG19610, U01AG046170, P50 AG025688, U01 AG046161, U01 AG061357]
- Translational Genomics Research Institute
- National Institute of Neurological Disorders and Stroke (NINDS) grant [R01 NS080820]
- CurePSP Foundation
- Mayo Foundation
- National Institute of Neurological Disorders and Stroke [U24 NS072026]
- Arizona Department of Health Services [211002]
- Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]
- Michael J. Fox Foundation for Parkinson's Research
- NIH [U01 AG046139, R01AG053960, R01AG050631, R01AG057339, U01AG046161, RF1AG054014, RF1 AG057440, R01AG057473, R01AG057914, P50 NS38377, F31AG050357]
- Cullen Foundation
- Baylor College of Medicine Medical Scientist Training Program (MSTP)
- Huffington Foundation
- Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital
- Burroughs Wellcome Fund
- National Science Foundation, Division of Mathematical Sciences [DMS-1263932]
- Cancer Prevention Research Institute of Texas [RP170387]
- Houston Endowment
- Neurodegeneration Consortium
- Belfer Family Foundation
- JPB Foundation
- Johns Hopkins Hospital [M-2014]
- Johns Hopkins University School of Medicine and the foundation's Parkinson's Disease Program [M-2014]
- NATIONAL INSTITUTE ON AGING [F31AG067677] Funding Source: NIH RePORTER
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available