Absence of Duplication of Chromosome 21 Genes in Familial and Sporadic Alzheimer's Disease

TLDR

The hypothesis that AD may arise from overexpression or duplication of chromosome 21 genes is supported by AD‑like pathology in Down syndrome and the mapping of familial AD and amyloid β to this autosome. The authors investigated potential duplication of chromosome 21 loci, including amyloid and SOD I, by applying restriction fragment length polymorphism analysis to familial and sporadic AD patients. No increased DNA dosage was found in brain or leukocytes of AD patients, duplication of these regions is rare, and no allelic association with AD was detected for the examined loci, undermining the chromosome 21 duplication hypothesis.

Abstract

The possibility that Alzheimer's disease (AD) is caused by overexpression or duplication of one or more genes on chromosome 21 has been raised by the observation of AD-like neuropathologic changes in individuals with Down syndrome and by the mapping of both the defect for familial AD and the amyloid β protein gene to this autosome. Possible duplication on chromosome 21 was investigated in both familial and sporadic AD by means of restriction fragment length polymorphisms for the amyloid and SOD I loci, as well as for DNA markers in the vicinity of the familial AD defect and in the critical Down syndrome region of chromosome 21. No evidence of increased DNA dosage was observed in either brain or leukocytes of patients with inherited or sporadic forms of AD. Duplication of these regions is therefore not a frequent event in either form of AD. Furthermore, no significant allelic association was detected between AD and any of the loci, including the amyloid and SOD I genes, providing no support for the hypothesis that defects in these specific genes are the primary cause of AD.