Viral Hypothesis and Antiviral Treatment in Alzheimer’s Disease
Purpose of Review
Viruses, particularly herpes simplex virus (HSV), may be a cause of Alzheimer’s disease (AD). The evidence supporting the viral hypothesis suggests that antiviral treatment trials, which have not been conducted, are warranted.
HSV1 (oral herpes) and HSV2 (genital herpes) can trigger amyloid aggregation, and their DNA is common in amyloid plaques. HSV1 reactivation is associated with tau hyperphosphorylation and possibly tau propagation. Anti-HSV drugs reduce Aβ and p-tau accumulation in infected mouse brains. Clinically, after the initial oral infection, herpes simplex virus-1 (HSV1) becomes latent in the trigeminal ganglion and recurrent reactivation may produce neuronal damage and AD pathology. Clinical studies show cognitive impairment in HSV seropositive patients, and antiviral drugs show strong efficacy against HSV.
An antiviral treatment trial in AD is clearly warranted. A phase II treatment trial with valacyclovir, an anti-HSV drug, recently began with evaluation of clinical and biomarker outcomes.
KeywordsAlzheimer’s disease Viral hypothesis Dementia Amyloid Tau Antiviral treatment
Compliance with Ethical Standards
Conflict of Interest
Davangere P. Devanand reports grants from the National Institute of Aging and Avanir and personal fees from Acadia, Eisai, Genetech, and Axovant.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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