title: High frequency of apolipoprotein E epsilon4 allele in young individuals with very mild Alzheimer's disease-related neurofibrillary changes.
abstract: The pathological process of initial neurofibrillary (NF) changes underlying Alzheimer's disease (AD) represents the early preclinical phase of the disease. In a small percentage of individuals, these initial NF changes (Braaks' stage I of six stages) may develop at a surprisingly young age. The aim of this study was to determine the impact of apolipoprotein E (ApoE) on the development of such initial NF changes in young individuals. To this end, the ApoE genotypes were determined using a seminested polymerase chain reaction assay followed by restriction isotyping in young individuals (n = 44; mean age of 38 years) with initial NF changes (stage I). The results were compared with ApoE genotypes of age-matched controls (n = 70) devoid of such changes (stage 0). Stage I cases exhibited a significantly higher epsilon4 allele frequency compared to controls (0.18 vs 0.09, P = 0.039). Thus, the present study reveals an association of epsilon4 allele with the early onset of AD-related NF changes in young individuals. This finding underlines the relevance of the asymptomatic phase in the course of AD.
authors.affiliation: Department of Anatomy, J. W. Goethe-University, Theodor Stern Kai 7, Frankfurt/Main, 60590, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Ghebremedhin
authors.forename: C
authors.initials: C
authors.lastname: Schultz
authors.forename: E
authors.initials: E
authors.lastname: Braak
authors.forename: H
authors.initials: H
authors.lastname: Braak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E