ApoE genotype is a risk factor in nonpresenilin early‐onset alzheimer's disease families

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. (C) 1998 Wiley-Liss, Inc.