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Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus.

Neuron | 2018

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.

Pubmed ID: 29937276 RIS Download

Associated grants

  • Agency: NIA NIH HHS, United States
    Id: RF1 AG058469
  • Agency: NIA NIH HHS, United States
    Id: U01 AG046152
  • Agency: NIA NIH HHS, United States
    Id: RF1 AG015819
  • Agency: NIBIB NIH HHS, United States
    Id: U54 EB020406
  • Agency: NIA NIH HHS, United States
    Id: P50 AG016574
  • Agency: NIA NIH HHS, United States
    Id: P30 AG010161
  • Agency: NIA NIH HHS, United States
    Id: R01 AG032990
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS080820
  • Agency: NIA NIH HHS, United States
    Id: U01 AG046139
  • Agency: NIA NIH HHS, United States
    Id: P01 AG017216
  • Agency: NIA NIH HHS, United States
    Id: R01 AG018023
  • Agency: NIA NIH HHS, United States
    Id: R56 AG058469
  • Agency: NIA NIH HHS, United States
    Id: U01 AG032984
  • Agency: NIA NIH HHS, United States
    Id: R01 AG030146
  • Agency: NIA NIH HHS, United States
    Id: U01 AG046170
  • Agency: NIA NIH HHS, United States
    Id: R01 AG017917
  • Agency: NIA NIH HHS, United States
    Id: R34 AG049649
  • Agency: NIA NIH HHS, United States
    Id: P01 AG003949
  • Agency: NINDS NIH HHS, United States
    Id: U24 NS072026
  • Agency: NIA NIH HHS, United States
    Id: P30 AG019610
  • Agency: NIA NIH HHS, United States
    Id: P50 AG025711
  • Agency: NIA NIH HHS, United States
    Id: U01 AG006786
  • Agency: NIA NIH HHS, United States
    Id: R01 AG036836
  • Agency: NIA NIH HHS, United States
    Id: R01 AG015819

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This is a list of tools and resources that we have found mentioned in this publication.


CRAN (tool)

RRID:SCR_003005

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RRID:SCR_002105

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RRID:SCR_012802

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RRID:SCR_001905

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RRID:MMRRC_034832-JAX

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RRID:IMSR_JAX:007745

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RRID:AB_2665520

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