Are cerebrovascular factors involved in Alzheimer's disease?

Recent epidemiological studies have shown that vascular risk factors may be involved in Alzheimer's disease (AD) as well as dementia in general. To in vestigate the relation between a vascular disorder and AD pathology, curren t criteria are defective because most depend on exclusion of a cerebrovascu lar disorder. Epidemiological studies have indicated the possibilities that arteriosclerosis, abnormal blood pressure, diabetes mellitus and smoking m ay be related to the pathogenesis of AD. As for the mechanism that vascular disorders influence AD, it is presumed that amyloid deposition may be caus ed by a vascular disorder. Alternatively, a vascular event may cause progre ssion of subclinical AD to a clinical stage. Insulin resistance and apolipo protein E may also be involved in these mechanisms. Our studies show that i schemia-induced the Alzheimer-associated gene presenilin 1 (PS1) and endopl asmic reticulum-stress, generated from a vascular disorder, may unmask clin ical AD symptoms caused by presenilin mutation, suggesting that a vascular factor might be involved in the onset of familial AD. (C) 2000 Elsevier Sci ence Inc. All rights reserved.