Absence of Linkage of Chromosome 21q21 Markers to Familial Alzheimer's Disease

TLDR

Alzheimer’s disease is the most common dementia in the elderly, its etiology remains unknown but inheritance is implicated, and recent studies suggest an autosomal dominant gene may reside on chromosome 21q21. Linkage analysis excluded association of familial Alzheimer’s disease with chromosome 21q21 markers, ruling out linkage at recombination fractions up to 0.17 for D21S1/D21S72 and 0.10 for the amyloid β gene, with apparent recombinants observed in several families. The absence of linkage to chromosome 21q21 markers demonstrates that familial Alzheimer’s disease is genetically heterogeneous.

Abstract

Alzheimer's disease is the most common form of dementia among the elderly population. Although the etiology is unknown, inheritance plays a role in the pathogenesis of the disease. Recent work indicates that an autosomal dominant gene for Alzheimer's disease is located on chromosome 21 at band q21. In the present study of a group of autopsy-documented kindreds, no evidence for linkage was found between familial Alzheimer's disease (FAD) and chromosome 21q21 markers (D21S1/D21S72 and the amyloid β gene). Linkage to the D21S1/D21S72 locus was excluded at recombination fractions (θ) up to 0.17. Linkage to the amyloid gene was excluded at θ = 0.10. Apparent recombinants were noted in two families for the amyloid gene and in five families for the D21S1/D21S72 locus. These data indicate that FAD is genetically heterogeneous.