title: ApoE genotype is a risk factor in nonpresenilin early-onset Alzheimer's disease families.
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.
authors.affiliation: Neurogenetics Laboratory, Mayo Clinic Jacksonville, Florida 32224, USA.
authors.forename: H
authors.initials: H
authors.lastname: Houlden
authors.forename: R
authors.initials: R
authors.lastname: Crook
authors.forename: H
authors.initials: H
authors.lastname: Backhovens
authors.forename: G
authors.initials: G
authors.lastname: Prihar
authors.forename: M
authors.initials: M
authors.lastname: Baker
authors.forename: M
authors.initials: M
authors.lastname: Hutton
authors.forename: M
authors.initials: M
authors.lastname: Rossor
authors.forename: J J
authors.initials: JJ
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: J
authors.initials: J
authors.lastname: Hardy
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis*; D009154:Mutation; D053764:Presenilin-1; D053766:Presenilin-2; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2