The goal of this application is to conduct further analyses in the investigators' large, population-based case-control study. All subjects entered the study between 1987 and 1996. Alzheimer's disease (AD) cases were identified with new AD associated symptoms and then given a complete diagnostic evaluation by research clinical investigators. Control subjects were randomly selected from the same health maintenance organization (HMO) as cases. They were of similar age and sex, intact cognitive status, and were enrolled concurrently. All subjects have been followed annually to verify disease and vital status. The investigators state that the case subjects are likely to reflect sporadic AD occurrence in the general population. Subject accrual is complete; data and biological specimens have been obtained and stored; and the HMO computerized pharmacy database (est. 1977) contains medication history. Environmental and genetic factors may both play a role in the etiology of AD. Apolipoprotein E (e4-allele containing genotypes; APOE) has been shown to increase susceptibility to AD, i.e., it is a strong risk factor. The investigators will describe whether having an e4-containing genotype modifies the risk associated with occupational solvents, anti-inflammatory medications, estrogen replacement, and cigarette smoking. Polymorphic cytochrome p450 and glutathione-s-transferase (GST) genes biotransform environmental substances such as solvents and cigarette smoke. Depending on the polymorphic form of the gene, the original substance can be transformed to either a neutral or a risky state. The investigators will examine whether AD association with solvents or cigarette smoking is modified by polymorphic forms of CYP1A1, CYP2D6, CYP2E1, and GST-T1. Further, the alpha-1-antichymotrypsin gene (2-allele system) may act together with APOE to modify the APOE-AD association (Kamboh et al., 1995). The investigators will compare the strength of association between AD and APOE-e4 across alpha-1-antichymotrypsin genotypes (described as AA, AT, TT).
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