title: Allelic variability in D21S11, but not in APP or APOE, is associated with cognitive decline in Down syndrome.
abstract: Genetic variation in the APOE gene and variation in chromosome 21 genotypes, including the APP locus, may influence age-associated cognitive decline in adults with Down syndrome. Molecular genetic and longitudinal neuropsychological analysis was performed for 41 unrelated Caucasian individuals (mean age 48.1 +/- 1.1 years (s.c.m.)) with free trisomy 21. Allele frequencies and genotype distributions were compared among subgroups with or without evidence of cognitive decline. Genetic variability at APOE and APP was not significantly associated with evidence of cognitive decline. However, aged individuals with Down syndrome, without evidence of cognitive decline, demonstrated unusual allelic variability at D21S11. These findings are discussed in the context of current hypotheses of Alzheimer-type dementia in Down syndrome and in the general population.
authors.affiliation: Imperial College School of Medicine, Kennedy Galton Centre, Northwick Park and St Mark's NHS Trust, Harrow, Middlesex, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: L
authors.initials: L
authors.lastname: Crayton
authors.forename: G E
authors.initials: GE
authors.lastname: Davies
authors.forename: C
authors.initials: C
authors.lastname: Oliver
authors.forename: J
authors.initials: J
authors.lastname: Powell
authors.forename: A J
authors.initials: AJ
authors.lastname: Holland
authors.forename: A M
authors.initials: AM
authors.lastname: Kessling
mesh_terms: D000328:Adult; D000367:Age Factors; D000483:Alleles; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D004314:Down Syndrome / Q000150:complications / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E