HLA class I, II & III genes in confirmed late-onset Alzheimer's disease

We first examined all the then known alleles (1997) at the HLA-A, B, Bw, C, DRB1, 3, 4 and 5, and DQB1 loci in 55 late-onset (>65y) AD eases and 73 el derly controls from Oxford. We found an association of HLA-B7 with late-ons et AD (odds ratio = 3.1, corrected P = 0.04) that was limited to apolipopro tein E epsilon4-negative subjects (odds ratio = 5.1, corrected P = 0.005). We then studied linkages with Class III genes and, finally, we sought to re plicate our HLA-B7 result in cohorts from Montreal and Nottingham. Altogeth er, we used 299 histopathologically confirmed cases of late-onset AD and 17 5 controls. Our initial, clear finding was not replicated in Montreal and N ottingham, however. We also failed to support any other previously reported association of AD with an HLA gene. Though we cannot exclude distinct link ages in different cohorts as an explanation of the conflicting results of H LNAD studies, we conclude that there is no compelling evidence of a strong, direct association between late-onset AD and any HLA Class I or II allele. (C) 2001 Elsevier Science Inc. All rights reserved.