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Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer's Disease but is not causative.
Am J Med Genet 1995; 60(1):1-6AJ

Abstract

An association has been observed in several independent data sets between late onset Alzheimer's Disease (AD) and the APOE locus on chromosome 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at-risk siblings of the FHP group we found an excess of the epsilon 4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and non-stringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease free survival suggested that APOE genotype contributes a small fraction of the total variance indicating that the APOE locus is a poor predictor of disease free survival age within late onset families. One explanation for the age dependent association reported by other groups, and our results, is that the APOE locus enhances the rate of progression of the disease process in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause the disease. We suggest this hypothesis is compatible with the current literature regarding APOE and AD.

Authors+Show Affiliations

Department of Psychiatry, University of South Florida, Tampa 33613, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7485228

Citation

Bennett, C, et al. "Evidence That the APOE Locus Influences Rate of Disease Progression in Late Onset Familial Alzheimer's Disease but Is Not Causative." American Journal of Medical Genetics, vol. 60, no. 1, 1995, pp. 1-6.
Bennett C, Crawford F, Osborne A, et al. Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer's Disease but is not causative. Am J Med Genet. 1995;60(1):1-6.
Bennett, C., Crawford, F., Osborne, A., Diaz, P., Hoyne, J., Lopez, R., ... Mullan, M. (1995). Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer's Disease but is not causative. American Journal of Medical Genetics, 60(1), pp. 1-6.
Bennett C, et al. Evidence That the APOE Locus Influences Rate of Disease Progression in Late Onset Familial Alzheimer's Disease but Is Not Causative. Am J Med Genet. 1995 Feb 27;60(1):1-6. PubMed PMID: 7485228.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer's Disease but is not causative. AU - Bennett,C, AU - Crawford,F, AU - Osborne,A, AU - Diaz,P, AU - Hoyne,J, AU - Lopez,R, AU - Roques,P, AU - Duara,R, AU - Rossor,M, AU - Mullan,M, PY - 1995/2/27/pubmed PY - 1995/2/27/medline PY - 1995/2/27/entrez SP - 1 EP - 6 JF - American journal of medical genetics JO - Am. J. Med. Genet. VL - 60 IS - 1 N2 - An association has been observed in several independent data sets between late onset Alzheimer's Disease (AD) and the APOE locus on chromosome 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at-risk siblings of the FHP group we found an excess of the epsilon 4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and non-stringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease free survival suggested that APOE genotype contributes a small fraction of the total variance indicating that the APOE locus is a poor predictor of disease free survival age within late onset families. One explanation for the age dependent association reported by other groups, and our results, is that the APOE locus enhances the rate of progression of the disease process in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause the disease. We suggest this hypothesis is compatible with the current literature regarding APOE and AD. SN - 0148-7299 UR - https://www.unboundmedicine.com/medline/citation/7485228/Evidence_that_the_APOE_locus_influences_rate_of_disease_progression_in_late_onset_familial_Alzheimer's_Disease_but_is_not_causative_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1995&volume=60&issue=1&spage=1 DB - PRIME DP - Unbound Medicine ER -