This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.During the 11 years of this project we demonstrated that genetic factors have a major role in the development of Alzheimer's disease (AD) among patients ascertained in clinical settings. We have also shown that the epsilon4 variant of apolipoprotein E (APOE), the strongest AD risk factor identified thus far, is more weakly associated with disease in men, persons older than 75 years, and several groups of non-European descent including African Americans. Our work also suggests that the influence of e4 on risk and age at onset of AD is modulated by the angiotensin converting enzyme (ACE) gene and several extrinsic factors including head trauma, alcohol use, parental age, and hypertension. There is a growing body of evidence from pathological, epidemiological, and genetic studies that risk factors for vascular disease also enhance risk of AD. However, since most epidemiological studies lack neuroimaging data, it is unclear whether the apparent association between vascular risk factors and AD is mediated via ischemic injury to the brain, acceleration of the primary Alzheimer neurodegenerative process, or some other process. Some vascular risk factors are more prevalent in African American and Japanese American populations than in Causcasians. We propose to build on our earlier work by evaluating the association between APOE, genes involved in vascular function, and other indicators of cerebrovascular health including blood pressure and structural brain imaging (MRI), and susceptibility to AD in these ethnic groups.
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