title: Evidence that PICALM affects age at onset of Alzheimer's dementia in Down syndrome.
abstract: It is known that individuals with Down syndrome develop Alzheimer's disease with an early age at onset, although associated genetic risk factors have not been widely studied. We tested whether genes that increase the risk of late-onset Alzheimer's disease influence the age at onset in Down syndrome using genome-wide association data for age at onset of dementia in a small sample of individuals (N = 67) with Down syndrome. We tested for association with loci previously associated with Alzheimer's disease risk and, despite the small size of the study, we detected associations with age at onset of Alzheimer's disease in Down syndrome with PICALM (β = 3.31, p = 0.011) and the APOE loci (β = 3.58, p = 0.014). As dementia in people with Down syndrome is relatively understudied, we make all of these data publicly available to encourage further analyses of the problem of Alzheimer's disease in Down syndrome.
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK. emma.3.jones@kcl.ac.uk
authors.forename: Emma L
authors.initials: EL
authors.lastname: Jones
authors.forename: Kin
authors.initials: K
authors.lastname: Mok
authors.forename: Marisa
authors.initials: M
authors.lastname: Hanney
authors.forename: Denise
authors.initials: D
authors.lastname: Harold
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sims
authors.forename: Julie
authors.initials: J
authors.lastname: Williams
authors.forename: Clive
authors.initials: C
authors.lastname: Ballard
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D004314:Down Syndrome / Q000150:complications / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D018401:Sample Size
chemical_list: D001057:Apolipoproteins E; D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human
keywords: APOE; Alzheimer’s disease; Down syndrome; Genome-wide association study; PICALM