Recent epidemiological studies have shown that vascular risk factors may be involved in
Alzheimer's disease (AD) as well as
dementia in general. To investigate the relation between a vascular disorder and AD pathology, current criteria are defective because most depend on exclusion of a
cerebrovascular disorder. Epidemiological studies have indicated the possibilities that
arteriosclerosis, abnormal blood pressure,
diabetes mellitus and smoking may be related to the pathogenesis of AD. As for the mechanism that vascular disorders influence AD, it is presumed that
amyloid deposition may be caused by a vascular disorder. Alternatively, a vascular event may cause progression of subclinical AD to a clinical stage.
Insulin resistance and
apolipoprotein E may also be involved in these mechanisms. Our studies show that
ischemia-induced the Alzheimer-associated gene
presenilin 1 (PS1) and endoplasmic reticulum-stress, generated from a vascular disorder, may unmask clinical AD symptoms caused by
presenilin mutation, suggesting that a
vascular factor might be involved in the onset of familial AD.