Journal
NEURON
Volume 99, Issue 1, Pages 64-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2018.05.023
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Funding
- NIA [U01AG046139, P50 AG016574, RO1 AG032990, U01 AG046139, R01 AG018023, U01 AG006576, U01 AG006786, R01 AG025711, RO1 AG017216, RO1 AG003949]
- NIH [U54EB020406]
- NINDS [RO1 NS080820]
- CurePSP Foundation
- Mayo Foundation
- National Institute of Neurological Disorders and Stroke [U24 NS072026]
- National Institute on Aging [P30 AG19610]
- Arizona Department of Health Services [211002]
- Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]
- Michael J. Fox Foundation for Parkinson's Research
- NIA grants [P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984, U01AG46152, U01 AG046170, 1R56AG058469]
- Illinois Department of Public Health
- Translational Genomics Research Institute
- Katherine Gehl
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Investigators have long suspected that pathogenic microbes might contribute to the onset and progression of Alzheimer's disease (AD) although definitive evidence has not been presented. Whether such findings represent a causal contribution, or reflect opportunistic passengers of neurodegeneration, is also difficult to resolve. We constructed multiscale networks of the late-onset AD-associated virome, integrating genomic, transcriptomic, proteomic, and histopathological data across four brain regions from human post-mortem tissue. We observed increased human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) from subjects with AD compared with controls. These results were replicated in two additional, independent and geographically dispersed cohorts. We observed regulatory relationships linking viral abundance and modulators of APP metabolism, including induction of APBB2, APPBP2, BIN1, BACE1, CLU, PICALM, and PSEN1 by HHV-6A. This study elucidates networks linking molecular, clinical, and neuropathological features with viral activity and is consistent with viral activity constituting a general feature of AD.
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