Previous research has indicated an association between the Histocompatibility Locus Antigen (HLA) A2 and men with the sporadic form of early-onset (less than 60 years) Alzheimer disease (AD). It is not known whether this finding can be generalized to a large sample, and the degree that lack of family history for AD defines the A2-positive subgroup: To fill such knowledge gaps, we propose to (1) perform HLA typing on 100 men with early-onset AD (50 with a family history of AD and 50 sporadic cases); (2) show that HLA-A2 and other relevant antigens have the expected-high frequency; and (3) determine if the A2 frequency is greater in sporadic than in familial AD. Thirteen of the National Institute on Aging AD Centers have agreed to provide blood from registered AD patients with research-level diagnoses. Enough blood will be drawn from each subject so that some will be stored for possible later DNA analyses, thus providing the basis for future studies exploring the molecular biology of A2 and closely linked genes. Because prior studies also indicate nongenetic factors influencing disease expression, differences among subgroups in frequencies of environmental risk factors will be explored. Identification of neurobiologically meaningful AD subgroups could facilitate future studies that elucidate disease etiology.
