Senile plaques in Alzheimer's diseased brains: possible association of beta-amyloid with herpes simplex virus type 1 (HSV-1) L-particles.
The characteristic insoluble, senile (neuritic) plaques found extracellularly in brains of patients with Alzheimer's disease (AD) contain the fibrillar form of beta-amyloid (Abeta42). 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) Abeta binds to L-particles; (2) Abeta 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 Abeta 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.
Kammerman
E M
EM
LSU Eye Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite B, New Orleans, LA 70112 2234, USA. elikam@comcast.net
Neumann
D M
DM
Ball
M J
MJ
Lukiw
Walter
W
Hill
J M
JM
D000544:Alzheimer Disease / Q000473:pathology* / Q000821:virology; D016229:Amyloid beta-Peptides / Q000502:physiology*; D001921:Brain / Q000473:pathology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D014771:Virion / Q000502:physiology*
D016229:Amyloid beta-Peptides