Alzheimer's disease as a viral disease: Revisiting the infectious hypothesis

Alzheimer's disease (AD) represents the most frequent type of dementia in elderly people. Two major forms of the disease exist: sporadic-the causes of which have not yet been fully understood -and familial-inherited within families from generation to generation, with a clear autosomal dominant transmission of mutations in Presenilin 1 (PSEN1), 2 (PSEN2) or Amyloid Precursors Protein (APP) genes. The main hallmark of AD consists of extra -cellular deposits of amyloid-beta (A beta) peptide and intracellular deposits of the hyperphosphorylated form of the tau protein. An ever-growing body of research supports the viral infectious hypothesis of sporadic forms of AD. In particular, it has been shown that several herpes viruses (i.e., HHV-1, HHV-2, HHV-3 or varicella zoster virus, HHV-4 or Epstein Barr virus, HHV-5 or cytomegalovirus, HHV-6A and B, HHV-7), flaviviruses (i.e., Zika virus, Dengue fever virus, Japanese encephalitis virus) as well as Human Immunodeficiency Virus (HIV), hepatitis viruses (HAV, HBV, HCV, HDV, HEV), SARS-CoV2, Ljungan virus (LV), Influenza A virus and Borna disease virus, could increase the risk of AD. Here, we summarized and discussed these results. Based on these findings, sig-nificant issues for future studies are also put forward.

Automated summary

This study summarizes and discusses the etiology of Alzheimer's disease and the hypothesis of viral infection. Viral infection may be an important factor in sporadic AD, including various herpes viruses, flaviviruses, and HIV.