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. 1998 Feb 7;81(1):117-21.
doi: 10.1002/(sici)1096-8628(19980207)81:1<117::aid-ajmg19>3.0.co;2-m.

ApoE genotype is a risk factor in nonpresenilin early-onset Alzheimer's disease families

H Houlden  1 , R Crook, H Backhovens, G Prihar, M Baker, M Hutton, M Rossor, J J Martin, C Van Broeckhoven, J Hardy
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ApoE genotype is a risk factor in nonpresenilin early-onset Alzheimer's disease families

H Houlden et al. Am J Med Genet. .

Abstract

The apolipoprotein E (ApoE) genotype is a significant risk factor and modulator of age of onset of Alzheimer's disease (AD). We analyzed the effect of the ApoE genotype in two distinct early-onset familial AD groups: families with a mutation in the presenilin-1 gene (PS-1) on chromosome 14, and families without a mutation detectable in the PS-1, presenilin-2 (PS-2), and the amyloid precursor protein (APP) gene (non-PS early-onset familial AD). The ApoE genotype is clearly shown not to modulate age of onset in families with a mutation in the PS-1 gene and families with no lesion detectable in either the presenilin or APP gene. The effects of a double dose of ApoE4 on age of onset were not assessed in the PS-1 AD families due to the lack of any affected ApoE4 homozygotes in the sample set; this insufficiency will need to be assessed in further studies. There was no association between the ApoE4 allele and AD in the PS-1 families. Non-PS early-onset AD families were shown to have a significantly higher frequency of ApoE4 compared to controls and the PS-1 AD group. These observations are important and suggest that 1) other genetic and environmental factors modify the AD phenotype in PS-1 and non-PS early-onset families; and 2) the ApoE4 allele is a significant risk factor in the etiology of non-PS early-onset AD and will be a useful adjunct in the diagnosis of unaffected family members.

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