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Pathological hallmarks of AD brains include senile plaques induced by amyloid \u03b2 peptide (A\u03b2) 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 A\u03b2 production, phosphorylation of tau (P\u2010tau), oxidative stress, neuroinflammation, etc. A\u03b2 peptide is regarded as one of the antimicrobial peptides, which inhibits HSV\u20101 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 A\u03b2 and P\u2010tau by impairing mitochondria and autophagosome. Epidemiological studies have shown AD susceptibility genes, such as APOE\u2010\u03b54 allele, are highly linked to infections by herpesviruses. Interestingly, anti\u2010herpesviral 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.<\/jats:p>","DOI":"10.1002\/jmv.25481","type":"journal-article","created":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T04:01:10Z","timestamp":1555560070000},"page":"1368-1377","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Herpesviral infections and antimicrobial protection for Alzheimer's disease: Implications for prevention and treatment"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6315-5809","authenticated-orcid":false,"given":"Qingsong","family":"Qin","sequence":"first","affiliation":[{"name":"Laboratory of Human Virology and Oncology Shantou University Medical College Shantou Guangdong 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