ALLELIC VARIABILITY IN D21S11, BUT NOT IN APP OR APOE, IS ASSOCIATED WITH COGNITIVE DECLINE IN DOWN-SYNDROME

GENETIC variation in the APOE gene and variation in chromosome 21 geno types, including the APP locus, may influence age-associated cognitive decline in adults with Down syndrome. Molecular genetic and longitudi nal neuropsychological analysis was performed for 41 unrelated Caucasi an individuals (mean age 48.1 +/- 1.1 years (s.e.m.)) with free trisom y 21. Allele frequencies and genotype distributions were compared amon g subgroups with or without evidence of cognitive decline. Genetic var iability at APOE and APP was not significantly associated with evidenc e of cognitive decline. However, aged individuals with Down syndrome, without evidence of cognitive decline, demonstrated unusual allelic va riability at D21S11. These findings are discussed in the context of cu rrent hypotheses of Alzheimer-type dementia in Down syndrome and in th e general population.