Chromosome 21, Trisomy 21, and Alzheimer’s Disease

Down’s syndrome is defined by a characteristic phenotype, mental retardation and associated pathological manifestations such as rapid aging and Alzheimer’s disease. In most cases, Down’s syndrome results from the presence of an extra chromosome 21 in all cells. Genes which in triplicate participate in Down’s syndrome pathology have yet to be found. Studies of partial trisomies have shown that they are in the distal part (21q21→q22) of chromosome 21. We are currently investigating several patients with most of the features of Down’s syndrome but an apparently normal karyotype. Enzymes coded by chromosome 21, namely superoxide dismutase (SOD) and cystathionine beta synthase, have been assessed, as well as gene copy number for the amyloid protein precursor, the protooncogene ETS2 and various anonymous DNA sequences. Results indicate that duplication of two regions might be important in Down’s syndrome pathogeny: one containing the SOD gene, the other the protooncogene ETS2.