Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer’s disease

Alzheimer's disease (AD) diagnosis relies on the presence of extracellular β-amyloid (Aβ) and intracellular hyperphosphorylated tau (p-tau). Emerging evidence suggests a potential link between AD pathologies and infectious agents, with herpes simplex virus 1 (HSV-1) being a leading candidate. Our investigation, using metagenomics, mass spectrometry, western blotting, and decrowding expansion pathology, detects HSV-1-associated proteins in human brain samples. Expression of the herpesvirus protein ICP27 increases with AD severity and strongly colocalizes with p-tau but not with Aβ. Modeling in human brain organoids shows that HSV-1 infection elevates tau phosphorylation. Notably, p-tau reduces ICP27 expression…

• FF
  Foundation for the National Institutes of Health

  Award: R56-AG069192-01
• UO
  University of Pittsburgh
• IS
  Israel Science Foundation

  Awards: 632/20, 654/20
• NI
  National Institutes of Health

  Award: R56-AG069192-01
• UO
  University of California, San Diego
• AD
  Alzheimer's Disease Research Center, University of Pittsburgh

  Award: P30-AG066468
• NI
  National Institute on Aging

  Award: P30 AG062429
• NI
  National Institute of Neurological Disorders and Stroke

  Awards: 1-R01-NS115082-01A1, 1-R21-NS096405-01A1