Herpesviral infections and antimicrobial protection for Alzheimer's disease: Implications for prevention and treatment.

Abstract

Accumulating evidence suggests that infections by herpesviruses might be closely linked to Alzheimer's disease (AD). Pathological hallmarks of AD brains include senile plaques induced by amyloid β peptide (Aβ) in the extracellular space and intracellular neurofibrillary tangles (NFTs) consisting of phosphorylated tau protein. The prevailing hypothesis for the mechanism of AD is amyloid cascade reaction. Recent studies revealed that infections by herpesviruses induce the similar pathological hallmarks of AD, including Aβ production, phosphorylation of tau (P-tau), oxidative stress, neuroinflammation, etc. Aβ peptide is regarded as one of the antimicrobial peptides, which inhibits HSV-1 replication. In the elderly, reactivation of herpesviruses might act as an initiator for amyloid cascade reaction in vulnerable individuals, triggering the neurofibrillary formation of phosphorylated tau and inducing oxidative stress and neuroinflammation, which can further contribute to the accumulation of Aβ and P-tau by impairing mitochondria and autophagosome. Epidemiological studies have shown AD susceptibility genes, such as APOE-ε4 allele, are highly linked to infections by herpesviruses. Interestingly, anti-herpesviral therapy significantly reduced the risk of AD in a large population study. Given that herpesviruses are arguably the most prevalent opportunistic pathogens and often reactivate in the elderly, it is reasonable to argue reactivation of herpesviruses might be major culprits for initiating AD in individuals carrying AD susceptibility genes. In this review, we summarize epidemiological and molecular evidence that support for a hypothesis of herpesviral infections and antimicrobial protection in the development of AD, and discuss the implications for future prevention and treatment of the disease.

• Authors: Qingsong Qin, Yun Li
• Journal: Journal of medical virology (J Med Virol) Vol. 91 Issue 8 Pg. 1368-1377 (08 2019) ISSN: 1096-9071 [Electronic] United States
• PMID: 30997676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• Amyloid beta-Peptides
• Immunologic Factors

Topics

• Alzheimer Disease (epidemiology, physiopathology, prevention & control, therapy)
• Amyloid beta-Peptides (metabolism, toxicity)
• Herpesviridae (immunology)
• Herpesviridae Infections (complications)
• Humans
• Immunologic Factors (metabolism, toxicity)
• Virus Activation