Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer's disease but is not causative

C. Bennett, F. Crawford, A. Osborne, P. Diaz, J. Hoyne, Roberto Lopez Alberola, P. Roques, R. Duara, M. Rossor, M. Mullan

Research output: Contribution to journalArticle

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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 examine 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 E4 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.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume60
Issue number1
DOIs
StatePublished - Mar 13 1995
Externally publishedYes

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Age of Onset
Disease-Free Survival
Disease Progression
Alzheimer Disease
Alleles
Genotype
Lod Score
Chromosomes, Human, Pair 19
Age Distribution
Gene Frequency
Analysis of Variance
Alzheimer disease type 2
Datasets

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer's disease but is not causative. / Bennett, C.; Crawford, F.; Osborne, A.; Diaz, P.; Hoyne, J.; Lopez Alberola, Roberto; Roques, P.; Duara, R.; Rossor, M.; Mullan, M.

In: American Journal of Medical Genetics - Neuropsychiatric Genetics, Vol. 60, No. 1, 13.03.1995, p. 1-6.

Research output: Contribution to journalArticle

Bennett, C. ; Crawford, F. ; Osborne, A. ; Diaz, P. ; Hoyne, J. ; Lopez Alberola, Roberto ; Roques, P. ; Duara, R. ; Rossor, M. ; Mullan, M. / Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer's disease but is not causative. In: American Journal of Medical Genetics - Neuropsychiatric Genetics. 1995 ; Vol. 60, No. 1. pp. 1-6.
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