ApoE-4 and age at onset of Alzheimer's disease: the NIMH genetics initiative
Abstract
To explore the impact of apoE-4 on Alzheimer's disease (AD) and its age at onset. A genetic linkage study using affected relative pairs, predominantly siblings. Three academic medical centers ascertained subjects from memory disorder clinics, nursing homes, and the local community. 310 families including 679 subjects with AD by NINCDS/ADRDA and/or Khachaturian criteria and 231 unaffected subjects. ApoE genotype. ANALYTIC METHODS: Association, affected pedigree member, sibling pair, and lod score analyses. ApoE-4 was strongly associated with AD in this sample (allele frequency = 0.46 vs. 0.14 in controls, p < 0.000001). Results of lod score, affected pedigree member analysis, and sib-pair analysis also supported apoE-4 as a risk factor for AD. When the sample was stratified on family mean age at onset, the risk conferred by apoE-4 was most marked in the 61 to 65 age group. Individuals with two copies of apoE-4 had a significantly lower age at onset than those with one or no copies (66.4 vs. 72.0, p < 0.001), but individuals with one copy did not differ from those with none. Within families, the individual with the earliest age at onset had, on average, significantly more apoE-4 alleles (p < 0.0001) than the individual with the l...Continue Reading
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