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Association of the apolipoprotein E epsilon 4 allele with clinical subtypes of autopsy-confirmed Alzheimer's disease.
Am J Med Genet 1994; 54(3):199-205AJ

Abstract

Consistent with previous reports, we observed a significant association of the APOE epsilon 4 allele with Alzheimer's Disease (AD) in a series of 91 autopsy-confirmed cases. The epsilon 4 allele frequency was higher in cases with a family history of AD-like dementia (0.54 +/- 0.07), although the epsilon 4 allele frequency in the AD cases with a negative family history (0.38 +/- 0.05) remained significantly greater than that for the non-AD control group (0.13 +/- 0.03). A similar increase in epsilon 4 allele frequency (0.54 +/- 0.07) was observed in the AD cases with amyloid angiopathy, compared to those who did not have amyloid angiopathy (0.36 +/- 0.04). Contrary to previous reports, no effect of the dosage of the epsilon 4 allele was found on the age of onset of dementia among the AD cases and, contrary to reports suggesting an association of epsilon 4 and atherosclerosis, the epsilon 4 allele frequency was similar in cases with or without concurrent brain infarcts. Modest but consistent correlations were observed between the dosage of epsilon 4 alleles and the cortical density of senile plaques, but not neurofibrillary tangles. The last finding suggests that the pathogenic events mediated by the epsilon 4 allele may be more directly involved in the formation of senile plaques, the identifying lesions in AD, than neurofibrillary tangles. A robust association of both the presence of an epsilon 4 allele and a family history of AD-like dementia with concurrent amyloid angiopathy occurred within our sample of AD cases. This association arose from an interaction of the epsilon 4 allele with a separate familial factor for which a family history of dementia served as a surrogate. These results suggest that amyloid angiopathy may be a common or central feature of a form of familial AD that is associated with the transmission of the APOE epsilon 4 allele.

Authors+Show Affiliations

Department of Psychiatry, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania 15213.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7810577

Citation

Zubenko, G S., et al. "Association of the Apolipoprotein E Epsilon 4 Allele With Clinical Subtypes of Autopsy-confirmed Alzheimer's Disease." American Journal of Medical Genetics, vol. 54, no. 3, 1994, pp. 199-205.
Zubenko GS, Stiffler S, Stabler S, et al. Association of the apolipoprotein E epsilon 4 allele with clinical subtypes of autopsy-confirmed Alzheimer's disease. Am J Med Genet. 1994;54(3):199-205.
Zubenko, G. S., Stiffler, S., Stabler, S., Kopp, U., Hughes, H. B., Cohen, B. M., & Moossy, J. (1994). Association of the apolipoprotein E epsilon 4 allele with clinical subtypes of autopsy-confirmed Alzheimer's disease. American Journal of Medical Genetics, 54(3), pp. 199-205.
Zubenko GS, et al. Association of the Apolipoprotein E Epsilon 4 Allele With Clinical Subtypes of Autopsy-confirmed Alzheimer's Disease. Am J Med Genet. 1994 Sep 15;54(3):199-205. PubMed PMID: 7810577.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of the apolipoprotein E epsilon 4 allele with clinical subtypes of autopsy-confirmed Alzheimer's disease. AU - Zubenko,G S, AU - Stiffler,S, AU - Stabler,S, AU - Kopp,U, AU - Hughes,H B, AU - Cohen,B M, AU - Moossy,J, PY - 1994/9/15/pubmed PY - 1994/9/15/medline PY - 1994/9/15/entrez SP - 199 EP - 205 JF - American journal of medical genetics JO - Am. J. Med. Genet. VL - 54 IS - 3 N2 - Consistent with previous reports, we observed a significant association of the APOE epsilon 4 allele with Alzheimer's Disease (AD) in a series of 91 autopsy-confirmed cases. The epsilon 4 allele frequency was higher in cases with a family history of AD-like dementia (0.54 +/- 0.07), although the epsilon 4 allele frequency in the AD cases with a negative family history (0.38 +/- 0.05) remained significantly greater than that for the non-AD control group (0.13 +/- 0.03). A similar increase in epsilon 4 allele frequency (0.54 +/- 0.07) was observed in the AD cases with amyloid angiopathy, compared to those who did not have amyloid angiopathy (0.36 +/- 0.04). Contrary to previous reports, no effect of the dosage of the epsilon 4 allele was found on the age of onset of dementia among the AD cases and, contrary to reports suggesting an association of epsilon 4 and atherosclerosis, the epsilon 4 allele frequency was similar in cases with or without concurrent brain infarcts. Modest but consistent correlations were observed between the dosage of epsilon 4 alleles and the cortical density of senile plaques, but not neurofibrillary tangles. The last finding suggests that the pathogenic events mediated by the epsilon 4 allele may be more directly involved in the formation of senile plaques, the identifying lesions in AD, than neurofibrillary tangles. A robust association of both the presence of an epsilon 4 allele and a family history of AD-like dementia with concurrent amyloid angiopathy occurred within our sample of AD cases. This association arose from an interaction of the epsilon 4 allele with a separate familial factor for which a family history of dementia served as a surrogate. These results suggest that amyloid angiopathy may be a common or central feature of a form of familial AD that is associated with the transmission of the APOE epsilon 4 allele. SN - 0148-7299 UR - https://www.unboundmedicine.com/medline/citation/7810577/Association_of_the_apolipoprotein_E_epsilon_4_allele_with_clinical_subtypes_of_autopsy_confirmed_Alzheimer's_disease_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1994&volume=54&issue=3&spage=199 DB - PRIME DP - Unbound Medicine ER -