Presenilin 1 and alpha-1-antichymotrypsin polymorphisms in Down syndrome: no effect on the presence of dementia.

As people with Down syndrome (DS) age, they are at greater risk for Alzheimer disease (AD) than the general population. It has been suggested that polymorphisms at the genes for presenilin-1 (PS-1) and alpha-1-antichymotrypsin (ACT) confer an increased risk for AD in the general population, and therefore potentially to AD in people with DS. We obtained DNA from 231 individuals with DS and 233 population controls. People with DS were evaluated for dementia. Allele frequencies at PS-1 and ACT polymorphisms in people with DS were compared to those in age-matched controls. There were no frequency differences between the control sample and DS sample for PS-1 or ACT alleles or genotypes. Similarly, there were no differences in allele frequencies between the demented and age-matched non-demented DS samples. However a higher frequency of PS-1 heterozygotes in the demented DS group was noted. We conclude that unlike the general population, neither PS-1 nor ACT polymorphisms appear to have a similar detrimental effect on dementia in DS. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:616-620, 1999.