title: Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome.
abstract: We examined the contribution of candidates genes for Alzheimer's disease (AD) to individual differences in levels of beta amyloid peptides in adults with Down syndrom, a population at high risk for AD. Participants were 254 non-demented adults with Down syndrome, 30-78 years of age. Genomic deoxyribonucleic acid was genotyped using an Illumina GoldenGate custom array. We used linear regression to examine differences in levels of Aβ peptides associated with the number of risk alleles, adjusting for age, sex, level of intellectual disability, race and/or ethnicity, and the presence of the APOE ε4 allele. For Aβ42 levels, the strongest gene-wise association was found for a single nucleotide polymorphism (SNP) on CAHLM1; for Aβ40 levels, the strongest gene-wise associations were found for SNPs in IDE and SOD1, while the strongest gene-wise associations with levels of the Aβ42/Aβ40 ratio were found for SNPs in SORCS1. Broadly classified, variants in these genes may influence amyloid precursor protein processing (CALHM1, IDE), vesicular trafficking (SORCS1), and response to oxidative stress (SOD1).
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA; G.H. Sergievsky Center, New York, NY, USA; Department of Epidemiology, Columbia University Medical Center, New York, NY, USA; Department of Psychiatry, Columbia University Medical Center, New York, NY, USA. Electronic address: ns24@cumc.columbia.edu.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schupf
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Lee
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA.
authors.forename: Naeun
authors.initials: N
authors.lastname: Park
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA.
authors.forename: Lam-Ha
authors.initials: LH
authors.lastname: Dang
authors.affiliation: Department of Psychology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Pang
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Yale
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: David Kyung-Taek
authors.initials: DK
authors.lastname: Oh
authors.affiliation: Department of Psychology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Krinsky-McHale
authors.affiliation: Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Edmund C
authors.initials: EC
authors.lastname: Jenkins
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, NY, USA.
authors.forename: José A
authors.initials: JA
authors.lastname: Luchsinger
authors.affiliation: Department of Psychology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Warren B
authors.initials: WB
authors.lastname: Zigman
authors.affiliation: Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Silverman
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tycko
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Kisselev
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Clark
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA; G.H. Sergievsky Center, New York, NY, USA; Department of Epidemiology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000097:blood*; D001057:Apolipoproteins E / Q000235:genetics; D015220:Calcium Channels / Q000235:genetics; D004247:DNA / Q000235:genetics*; D004314:Down Syndrome / Q000097:blood* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D006801:Humans; D016014:Linear Models; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010446:Peptide Fragments / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics; D012306:Risk; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; C530077:CALHM1 protein, human; D015220:Calcium Channels; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C000606290:SOD1 protein, human; C472780:SORCS1 protein, human; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D004247:DNA; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Biomarkers; Down syndrome; Genetics; β Amyloid peptides