title: CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology.
abstract: In our functional dissection of the CD33 Alzheimer's disease susceptibility locus, we found that the rs3865444(C) risk allele was associated with greater cell surface expression of CD33 in the monocytes (t50 = 10.06, P(joint) = 1.3 × 10(-13)) of young and older individuals. It was also associated with diminished internalization of amyloid-β 42 peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Bradshaw
authors.forename: Lori B
authors.initials: LB
authors.lastname: Chibnik
authors.forename: Brendan T
authors.initials: BT
authors.lastname: Keenan
authors.forename: Linda
authors.initials: L
authors.lastname: Ottoboni
authors.forename: Towfique
authors.initials: T
authors.lastname: Raj
authors.forename: Anna
authors.initials: A
authors.lastname: Tang
authors.forename: Laura L
authors.initials: LL
authors.lastname: Rosenkrantz
authors.forename: Selina
authors.initials: S
authors.lastname: Imboywa
authors.forename: Michelle
authors.initials: M
authors.lastname: Lee
authors.forename: Alina
authors.initials: A
authors.lastname: Von Korff
authors.forename: Martha C
authors.initials: MC
authors.lastname: Morris
authors.forename: Denis A
authors.initials: DA
authors.lastname: Evans
authors.forename: Keith
authors.initials: K
authors.lastname: Johnson
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D060825:Cognitive Dysfunction / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D003911:Dextrans / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006681:HLA-D Antigens / Q000378:metabolism; D006801:Humans; D008297:Male; D017628:Microglia / Q000473:pathology; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics; D011877:Radionuclide Imaging; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000235:genetics / Q000378:metabolism*; D013844:Thiazoles; D055815:Young Adult
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D003911:Dextrans; D006681:HLA-D Antigens; D010446:Peptide Fragments; D063268:Sialic Acid Binding Ig-like Lectin 3; D013844:Thiazoles; C075222:amyloid beta-protein (1-42)