Chromosome-12 mapping of late-onset Alzheimer disease among Caribbean Hispanics

Linkage to chromosome 12p for familial Alzheimer disease (AD) has been inco nsistent. Using 35 markers near the centromere of chromosome 12, we investi gated 79 Caribbean Hispanic families with AD. Two-point linkage analysis us ing affected sib pairs yielded LOD scores of 3.15 at D12S1623 and 1.43 at D 12S1042. The LOD score at D12S1623 decreased to 1.62 in families with late- onset (age > 65 years) AD (LOAD), but the LOD score at D12S1042 was unchang ed. Among families negative for the apolipoprotein E (APOE-epsilon4) allele , the LOD score for D12S1623 was lower (1.01), whereas that for D12S1042 in creased to 1.73. Among families positive for the APOE-epsilon4 allele, none of the LOD scores reached 1. Multipoint affected-relative-pair analysis sh owed peaks at D12S1623 (nonparametric linkage [NPL] score 1.52; P = .028) a nd near D12S1042, at D12S1057 (NPL score 1.57; P = .027). NPL scores for bo th D12S1623 and D12S1057 increased in families affected with LOAD, but, in APOE-epsilon4-negative families, only scores for the region flanking D12S16 23 remained elevated (NPL score 1.74; P = .013). This study of Caribbean Hi spanics with familial AD extends and provides modest evidence of linkage to loci on chromosome 12p. Linkage varied by age at onset of AD and by the pr esence or absence of the APOE-epsilon4 allele.