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Are cerebrovascular factors involved in Alzheimer's disease?
T Kudo1, K Imaizumi, H Tanimukai
1Department of Clinical Neuroscience, Psychiatry, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan. kudo@psy.med.osaka-u.ac.jp
Insights
Vascular risk factors are linked to Alzheimer's disease (AD) pathogenesis. Our research indicates that vascular disorders, like ischemia, may trigger clinical AD symptoms in those with presenilin mutations.
Area of Science:
- Neuroscience
- Vascular Biology
- Gerontology
Background:
- Epidemiological studies suggest a link between vascular risk factors and Alzheimer's disease (AD) and general dementia.
- Current diagnostic criteria for AD often exclude cerebrovascular disorders, potentially masking underlying connections.
- Arteriosclerosis, hypertension, diabetes mellitus, and smoking are implicated in AD pathogenesis.
Purpose of the Study:
- To investigate the relationship between vascular disorders and Alzheimer's disease (AD) pathology.
- To explore potential mechanisms by which vascular issues influence AD development.
- To examine the role of vascular factors in the onset of familial AD.
Main Methods:
- Review of epidemiological data on vascular risk factors and AD.
- Analysis of proposed mechanisms, including amyloid deposition and vascular events.
- Experimental studies investigating ischemia-induced effects on AD-associated genes and endoplasmic reticulum stress.
Main Results:
- Vascular disorders are hypothesized to cause amyloid deposition or accelerate subclinical AD progression.
- Insulin resistance and apolipoprotein E are considered potential contributing factors.
- Our studies demonstrate that ischemia-induced endoplasmic reticulum stress can unmask clinical AD symptoms in presenilin mutation carriers.
Conclusions:
- Vascular factors may play a significant role in the onset of Alzheimer's disease, particularly familial AD.
- Ischemia and associated endoplasmic reticulum stress can precipitate clinical symptoms in individuals with underlying AD pathology.
- Further research is warranted to elucidate the complex interplay between vascular health and AD pathogenesis.
Abstract:
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.