The overall goal is to determine the chromosomal localization of the gene causing familial Alzheimer's disease (FAD) using genetic linkage to DNA markers. We shall obtain family histories from all patients attending the Memory Disorders Unit at the Massachusetts General Hospital. From these histories, we shall complete comprehensive pedigrees on families of patients with AD who have multiple demented ancestors and siblings. The diagnosis of AD in the index cases will be established by contemporary research criteria. We shall obtain blood samples from all living individuals in FAD families for preparation of genomic DNA and establishment of permanent lymphoblastoid cell lines. The banked cells will serve as a permanent source of DNA for subsequent molecular analysis. We shall analyze subjects' DNA for segregation of DNA markers; initial emphasis will be placed upon markers derived from chromosome 21 and later, involve other regions of the genome if necessary. We shall use standard linkage techniques in order to link DNA markers to the FAD locus. Characterization of the FAD gene sequence and product would lead to an understanding of the basis for familial AD, afford insights into sporadic AD, and might allow the development of effective therapies for AD. Related benefits to society would include clinical information on such issues as the proportion of AD cases with and without a family history of dementia (any first degree relative demented), and whether patterns of inheritance of AD are related to familial age at onset, whether the sex of an affected parent influences risk of inheritance, and whether other illnesses are commonly associated with AD.
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