Neuropathological epidemiology of cerebral aging: a study of two genetic polymorphisms

We studied whether ApoE and -219 GT (ApoE promoter) polymorphism modulates neurofibrillary tangle (NFT) and senile plaque (SP) development in aging am ong 190 non-institutionalized individuals (mean age 79.5 years). Analysis r evealed that the mean Braak stage was higher in is an element of4 allele ca rriers. Once individuals with Braak stage V were excluded (n = 5), relation ships between NFT and the two genotypes studied were weak, whereas in is an element of4 allele carriers, the risk of SP was multiplied by 4 to 7 in fo ur areas (CA1, subiculum, isocortex and entorhinal cortex). This associatio n was more pronounced in subjects under 80 years and was also observed when analysis was restricted to Braak stages 0, I and II. Epsilon 2 allele carr iers appeared to have fewer lesions but, due to limited numbers, this trend was not significant. In two regions (CAI, subiculum), the number of SP inc reased significantly for individuals who were homozygous for the T allele o f -219 GT. However the association was no longer significant when controlli ng for ApoE is an element of4. It should be noted that the brain of elderly subjects carrying one is an element of4 allele may not undergo senile chan ges. (C) 2001 Elsevier Science Inc. All rights reserved.