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

Kammerman, E.M.; Neumann, D.M.; Ball, M.J.; Lukiw, Walter; Hill, J.M.

doi:10.1016/j.mehy.2005.07.033

« Previous Next »Medical Hypotheses
Volume 66, Issue 2 , Pages 294-299, 2006

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

E.M. Kammerman
- LSU Eye Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite B, New Orleans, LA 70112 2234, USA
- Corresponding author. Tel.: +1 917 991 7994; fax: +1 504 412 1315.
D.M. Neumann
- LSU Eye Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite B, New Orleans, LA 70112 2234, USA
M.J. Ball
- Department of Pathology (Neuropathology), School of Medicine, Oregon Health and Science University, Portland, OR, USA
Walter Lukiw
- Department of Neuroscience, Louisiana State University Health Sciences Center, New Orleans, LA, USA
J.M. Hill
- LSU Eye Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite B, New Orleans, LA 70112 2234, USA
- Department of Neuroscience, Louisiana State University Health Sciences Center, New Orleans, LA, USA
- Departments of Pharmacology and Microbiology, Louisiana State University Health Sciences Center, New Orleans, LA, USA

Received 21 July 2005; accepted 25 July 2005. published online 19 October 2005.

Summary

The 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.