Alzheimer's disease-associated β-Amyloid does not protect against Herpes Simplex Virus 1 brain infection

Abstract

Alzheimers disease (AD) is devastating fatal neurodegenerative disease. An alternative to the amyloid cascade hypothesis is the hypothesis that a viral infection is key to the etiology of late-onset AD, with amyloid A{beta} peptides playing a protective role. Contrary to previous work, in the current study the 5XFAD genotype failed to protect mice against infection with two strains of herpes simplex virus 1 (HSV-1), 17syn+ and McKrae. Moreover, the region- or cell-specific tropisms of HSV-1 were not affected by the 5XFAD genotype, arguing that host-pathogen interactions were not altered. In aged 5XFAD mice with abundant A{beta} plaques, only small, statistically non-significant protection against acute HSV-1 infection was observed, yet no colocalization between HSV-1 and A{beta} plaques was found. While the current study questions the antiviral role of APP or A{beta}, it neither supports nor refutes the viral etiology hypothesis of late-onset AD.