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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Genotype
  • Humans
  • Membrane Proteins / analysis*
  • Mutation
  • Presenilin-1
  • Presenilin-2
  • Risk Factors


  • Apolipoprotein E4
  • Apolipoproteins E
  • Membrane Proteins
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Presenilin-1
  • Presenilin-2