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Previous Volume 333:1242-1248 November 9, 1995 Number 19 Next

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ABSTRACT

Background The 4 allele of apolipoprotein E has been associated with an increased risk of late-onset Alzheimer's disease. In a cohort of elderly subjects we prospectively investigated the relation between the apolipoprotein E genotype, dementia, and the accumulation of -amyloid protein in the cerebral cortex.

Methods Autopsy involving neuropathological analysis and DNA analysis of frozen blood samples was performed in 92 of 271 persons who were at least 85 years of age, who had been living in Vantaa, Finland, on April 1, 1991, and who had died between that time and the end of 1993. All subjects had been tested for dementia. Apolipoprotein E genotyping was done with a solid-phase minisequencing technique. The percentage of the cortex occupied by methenamine silver–stained plaques was used as an estimate of the extent of -amyloid protein deposition.

Results The frequency of the 4 allele was significantly higher in the subjects with Alzheimer's disease than in the subjects without dementia (30 percent vs. 8 percent, P<0.001). There was a greater accumulation of -amyloid protein in the brain and more neurofibrillary tangles in the subjects with the 4 allele than in those without it (P<0.001). The deposition of -amyloid protein varied according to the genotype in both the subjects with dementia and those without dementia: it was lowest in those with the 2/3 genotype, intermediate in those with the 3/3 genotype, and highest in those with the 3/4 genotype. A single subject had the 4/4 genotype and had dementia.

Conclusions The 4 allele of apolipoprotein 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 -amyloid protein in the cerebral cortex.

Source Information

From the Departments of Pathology (T.P., M.H.), Medicine (K. Kainulainen, A. Vuorio, K. Kontula), and Neurology (A. Verkkoniemi), University of Helsinki, Helsinki; the Department of Community Health and General Practice, University of Kuopio, Kuopio (R.S., P.H.); and Katariina Geriatric Hospital, Vantaa (L.N.) — all in Finland.

Address reprint requests to Dr. Polvikoski at the Department of Pathology, University of Helsinki, P.O. Box 21 (Haartmaninkatu 3), FIN-00014 Helsinki, Finland.

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N Engl J Med 1996; 334:599-600, Feb 29, 1996. Correspondence

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