Neurotropic viruses and Alzheimer disease. Interaction of herpes simplex type 1 virus and apolipoprotein E in the etiology of the disease.

Infectious agents have been proposed as possible etiological factors in sporadic cases of Alzheimer disease (AD), herpes simplex type 1 virus (HSV1) being a likely candidate. We have detected laten HSV1 in brain from AD patients and from aged normal individuals, using polymerase chain reaction (PCR), in the regions most affected in the disease. In contrast, we have not detected another neurotropic herpes virus, varicella zoster (VZV), in any brains. We have postulated that HSV1 reactivates periodically, and that a host or viral characteristic determines the degree of damage caused by the resulting acute infection-with much greater damage in the case of AD patients. We have therefore examined a host factor-the apolipoprotein E (apoE) genotype, since the E4 allele is a known risk factor in the disease. We have found that the risk of developing AD is much greater in those who are HSV1-positive in brain and who possess an apoE4 allele than for those with only one of these factors.