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Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein.
N Engl J Med 1995; 333(19):1242-7NEJM

Abstract

BACKGROUND

The epsilon 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 beta-amyloid protein in the cerebral cortex.

METHODS

Autopsy involving neuropathological analysis and DNA analysis of frozen blood samples were 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 beta-amyloid protein deposition.

RESULTS

The frequency of the epsilon 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 beta-amyloid protein in the brain and more neurofibrillary tangles in the subjects with the epsilon 4 allele than in those without it (P < 0.001). The deposition of beta-amyloid protein varied according to the genotype in both the subjects with dementia and those without dementia: it was lowest in those with the epsilon 2/epsilon 3 genotype, intermediate in those with the epsilon 3/epsilon 3 genotype, and highest in those with the epsilon 3/epsilon 4 genotype. A single subject had the epsilon 4/epsilon 4 genotype and had dementia.

CONCLUSIONS

The epsilon 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 beta-amyloid protein in the cerebral cortex.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7566000

Citation

Polvikoski, T, et al. "Apolipoprotein E, Dementia, and Cortical Deposition of Beta-amyloid Protein." The New England Journal of Medicine, vol. 333, no. 19, 1995, pp. 1242-7.
Polvikoski T, Sulkava R, Haltia M, et al. Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein. N Engl J Med. 1995;333(19):1242-7.
Polvikoski, T., Sulkava, R., Haltia, M., Kainulainen, K., Vuorio, A., Verkkoniemi, A., ... Kontula, K. (1995). Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein. The New England Journal of Medicine, 333(19), pp. 1242-7.
Polvikoski T, et al. Apolipoprotein E, Dementia, and Cortical Deposition of Beta-amyloid Protein. N Engl J Med. 1995 Nov 9;333(19):1242-7. PubMed PMID: 7566000.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein. AU - Polvikoski,T, AU - Sulkava,R, AU - Haltia,M, AU - Kainulainen,K, AU - Vuorio,A, AU - Verkkoniemi,A, AU - Niinistö,L, AU - Halonen,P, AU - Kontula,K, PY - 1995/11/9/pubmed PY - 1995/11/9/medline PY - 1995/11/9/entrez SP - 1242 EP - 7 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 333 IS - 19 N2 - BACKGROUND: The epsilon 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 beta-amyloid protein in the cerebral cortex. METHODS: Autopsy involving neuropathological analysis and DNA analysis of frozen blood samples were 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 beta-amyloid protein deposition. RESULTS: The frequency of the epsilon 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 beta-amyloid protein in the brain and more neurofibrillary tangles in the subjects with the epsilon 4 allele than in those without it (P < 0.001). The deposition of beta-amyloid protein varied according to the genotype in both the subjects with dementia and those without dementia: it was lowest in those with the epsilon 2/epsilon 3 genotype, intermediate in those with the epsilon 3/epsilon 3 genotype, and highest in those with the epsilon 3/epsilon 4 genotype. A single subject had the epsilon 4/epsilon 4 genotype and had dementia. CONCLUSIONS: The epsilon 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 beta-amyloid protein in the cerebral cortex. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/7566000/Apolipoprotein_E_dementia_and_cortical_deposition_of_beta_amyloid_protein_ L2 - http://www.nejm.org/doi/full/10.1056/NEJM199511093331902?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -