Alzheimer's disease (AD) is the most common cause of irreversible, chronic dementia. Although AD may be familial in only one third of all cases, the main justification for studying autosomal dominant cases lies in the accuracy of diagnosis which may be inferred through post-mortem examination of other affected family members. More than 200 members of 12 pedigrees with an autosomal dominant form of AD have had skin fibroblast and peripheral blood lymphoblast cultures established. These cultures serves as a renewable source of DNA and cell lines for genetic linkage, viability, and biochemical studies. Recombinant DNA technology has been applied to perform genetic linkage studies in these families with inherited AD. Additional families have provided further confirmation of our earlier identification of a region of chromosome 21 that is linked to AD and it appears that a single marker may soon be localize. There is no evidence for microduplication of chromosome 21 in either sporadic or familial cases of AD. CSF levels of acetylcholinesterase, a potential marker of central cholinergic function, are lower than normal in affected family members. Dermatoglyphic analysis has revealed an increased number of ulnar loops in the AD patients; a similar pattern has been observed in approximately half of the at-risk subjects. Although the AD patients have reductions in the rate of regional cerebral glucose metabolism, no definite changes have been identified in a longitudinal study of at-risk family members. A single genetic marker for AD will facilitate analysis of any neurochemical and metabolic changes in at-risk subjects since they can be grouped according to whether they carry the AD gene.
