This proposal is concerned with the development and the application of statistical techniques for examining age onset in familial Alzheimer's disease. Its activities will include extensive studies of the performance of both existing and newly developed methodology. A particular focus will be the extension of extant methodology to meet the specific needs of late onset disorders in general and Alzheimer's disease in particular, especially with respect to adjustment for ascertainment of families nd consideration of familial interrelationships. Specific goals include the delineation of the age of onset distribution(s) associated with familial Alzheimer's disease, evaluation of possible heterogeneity in age of onset among AD families, and examination of the question of familial correlations with respect to age of onset. A further goal is the integration of the developed models and techniques into existing procedures for the analysis of family data. These methodologies will be applicable to any familial disorder characterized by delayed onset, which may or may not have a genetic component; however, the particular focus of these investigations is the exploration of the age of onset phenomenon in familial Alzheimer's disease. These investigations will therefore provide tools to study variation in onset patterns in familial Alzheimer's disease to provide appropriate descriptors of age of onset distributions for use in genetic analyses, to identify factors associated with varying patterns in the onset of familial AD, to refine estimates of risk, and eventually to gain some insight into them mechanisms governing age of onset.
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