One hundred years ago dementing illnesses were classified based upon their clinical presentation and neuropathology. T he promise of the twenty first century is that w e w ill be able to classify these same diseases by t he genetic cause or genetic risk factors, a classification based upon etiology not symptomatology. During the last two decades mutations in many genes have been shown to cause Inherited forms of early onset dementing illnesses. These rare disorders have provided enormous insight into the pathogenesis of more common variants of the same diseases. A growing realization of the importance of genetic risk factors for common diseases has led the research community to assess the role of genetic as well as environmental risk factors in susceptibility for late onset Alzheimer's disease. In 1993, polymorphism in t he apolipoprotein E (APOE) gene w as shown to be the first identified risk factor for AD. A dose-dependent effect o f t he AP0E4 allele has been observed in al most every population studied. APOE genotype has now become an important variable in clinical and pathological studies of AD. Indeed, all clinical trials now evaluate putative AD drugs in AP0E4 positive and AP0E4 negative patient subgroups. The goal of the Genetics Core of the Washington University ADRC is to provide genetic information and useful materials on all ADRC participants. In the case of late onset AD we will obtain family history data, APOE genotypes and bank plasma and serum samples. This data will be stored in the master ADRC database and provided to investigators upon request and thus specifically will support Projects 1 (Perrin) and 3 (Bateman) of this competing renewal application. When new genetic risk factors are identified we will also provide this information where possible. In the case of multiplex kindreds we will collect family history data and screen individuals for mutations in the known dementia causing genes. Cell lines and brains from these individuals will be available for molecular studies on the effects of specific mutations.

Public Health Relevance

Alzheimer?s disease is a major public health problem. Currently we treat the symptoms of the disease but not the cause. The Genetics Core provides collects biological samples from ADRC participants and provides information about established genetic risk factors in these samples. This will help in assessing risk for disease and potentially in determining the optimal therapeutic approach in the future.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Specialized Center (P50)
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Special Emphasis Panel (ZAG1-ZIJ-4)
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Washington University
Saint Louis
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