Chromosome 14 and late-onset familial Alzheimer disease (FAD)

摘要: Familial Alzheimer disease (FAD) is genetically heterogeneous. Two loci responsible for early-onset FAD have been identified: the amyloid precursor protein gene on chromosome 21 and as-yet-unidentified locus 14. The genetics of late-onset unresolved. Maximum-likelihood, affected-pedigree-member (APM), sib-pair analyses were used, in 49 families with a mean age at onset ≥60 years, to determine whether 14 FAD. markers used D14S53, D14S43, D14S52. LOD score method was test linkage markers, under three different models: age-dependent penetrance, an affected-only analysis, penetrance allowance possible sporadic cases. No evidence obtained any these conditions kindreds, strong against (LOD ≤ –2.0) this region obtained. Heterogeneity tests results combined group (early onset, Volga Germans, late onset) favored hypothesis genetic heterogeneity. positive are primarily from families. APM analysis gave significant D14S43 D14S52 kindreds (P < .02). found entire family group. Significant D14S52, however, subgroup intermediate (mean years <70 years). These indicate that not most but could play role subset kindreds.