Senile plaques in Alzheimer’s diseased brains: Possible association of β-amyloid with herpes simplex virus type 1 (HSV-1) L-particles

SummaryThe characteristic insoluble, senile (neuritic) plaques found extracellularly in brains of patients with Alzheimer’s disease (AD) contain the fibrillar form of β-amyloid (Aβ42). A substantial proportion of autopsied elderly brains have demonstrated DNA evidence of herpes simplex virus type 1 (HSV-1) infiltration. HSV-1-infected cells produce significant quantities of non-infectious, non-DNA-containing light particles (L-particles) comprised of viral envelope and tegument proteins. HSV-induced L-particles can be exocytosed out of their host cells. This report advances the hypothesis that (1) Aβ binds to L-particles; (2) Aβ permeabilizes L-particles, destroying the integrity of the envelope and allowing the contained tegument proteins to spill into the extracellular space; and (3) these events are followed by a conformational shift of Aβ into its fibrillar form, physically trapping the L-particle-derived substances and resulting in the plaques characteristic of AD. These hypotheses are supported by reports of biomolecular changes and pathophysiologies which have been simultaneously observed in both AD- and HSV-infected brains.