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

Journal Article · Mon Feb 27 04:00:00 EST 1995 · American Journal of Medical Genetics

DOI:https://doi.org/10.1002/ajmg.1320600102· OSTI ID:443794

Bennett, C; Crawford, F; Osborne, A; Diaz, P ^[1]

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1. Univ. of South Florida, Tampa, FL (United States); and others

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. 19 refs., 1 fig., 2 tabs.

• Sponsoring Organization: USDOE
• OSTI ID: 443794
• Journal Information: American Journal of Medical Genetics, Journal Name: American Journal of Medical Genetics Journal Issue: 1 Vol. 60; ISSN 0148-7299; ISSN AJMGDA
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
AGE DEPENDENCE
BIOLOGICAL MARKERS
ETIOLOGY
GENES
GENETIC MAPPING
GENOTYPE
HEREDITARY DISEASES
HUMAN CHROMOSOME 19
MAN
NERVOUS SYSTEM DISEASES
STATISTICS