APOE IS LINKED TO ALZHEIMERS-DISEASE IN A LARGE PEDIGREE

Although previous association studies have demonstrated that the APOE4 allele is a risk factor for Alzheimer's disease (AD), its value for t he prediction of AD in individuals is <100%. The limited predictive va lue of epsilon 4 is also seen in multiply affected families where the epsilon 4 allele is not tightly linked to AD, We analyzed a large pedi gree multiply affected with AD by lod score linkage analysis at the kn own loci associated with AD, In this pedigree, the APOE/APOCI gene are a was linked to the development of AD, while no linkage was detected t o any of the other loci known to be associated with the disease, In th is family, then, the inheritance of an epsilon 4 allele is highly asso ciated with the early development of the disease (mean age of onset, 6 2 years), and is a good predictor of disease, However, given the wealt h of evidence for association, but not linkage, of APOE4 to AD, we bel ieve this finding suggests that another factor (or factors) interact(s ) with APOE to precipitate early disease, and produce positive linkage results, The nature of this factor presently remains unknown. (C) 199 7 Wiley-Liss, Inc.