APOLIPOPROTEIN-E, DEMENTIA, AND CORTICAL DEPOSITION OF BETA-AMYLOID PROTEIN

Background. The epsilon 4 allele of apolipoprotein E has been associat ed with an increased risk of late-onset Alzheimer's disease. In a coho rt of elderly subjects we prospectively investigated the relation betw een the apolipoprotein E genotype, dementia, and the accumulation of b eta-amyloid protein in the cerebral cortex. Methods. Autopsy involving neuropathological analysis and DNA analysis of frozen blood samples w as performed in 92 of 271 persons who were at least 85 years of age, w ho had been living in Vantaa, Finland, on April 1, 1991, and who had d ied between that time and the end of 1993. All subjects had been teste d for dementia, Apolipoprotein E genotyping was done with a solid-phas e minisequencing technique. The percentage of the cortex occupied by m ethenamine silver-stained plaques was used as an estimate of the exten t of beta-amyloid protein deposition. Results. The frequency of the ep silon 4 allele was significantly higher in the subjects with Alzheimer 's disease than in the subjects without dementia (30 percent vs, 8 per cent, P<0.001), There was a greater accumulation of beta-amyloid prote in in the brain and more neurofibrillary tangles in the subjects with the epsilon 4 allele than in those without it (P<0.001), The depositio n of beta-amyloid protein varied according to the genotype in both the subjects with dementia and those without dementia: it was lowest in t hose with the epsilon 2/epsilon 3 genotype, intermediate in those with the epsilon 3/epsilon 3 genotype, and highest in those with the epsil on 3/epsilon 4 genotype. A single subject had the epsilon 4/epsilon 4 genotype and had dementia. Conclusions. The epsilon 4 allele of apolip oprotein E is significantly associated with Alzheimer's disease. Even in elderly subjects without dementia, the apolipoprotein E genotype is related to the degree of deposition of beta-amyloid protein in the ce rebral cortex.