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Nat Neurosci DOI:10.1038/nn.3435

CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology.

Publication TypeJournal Article
Year of Publication2013
AuthorsBradshaw, EM, Chibnik, LB, Keenan, BT, Ottoboni, L, Raj, T, Tang, A, Rosenkrantz, LL, Imboywa, S, Lee, M, Von Korff, A, Morris, MC, Evans, DA, Johnson, K, Sperling, RA, Schneider, JA, Bennett, DA, De Jager, PL
Corporate AuthorsAlzheimer Disease Neuroimaging Initiative
JournalNat Neurosci
Volume16
Issue7
Pages848-50
Date Published2013 Jul
ISSN1546-1726
KeywordsAdult, Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Aniline Compounds, Brain, Cognitive Dysfunction, Cohort Studies, Dextrans, Female, Genetic Association Studies, Genotype, HLA-D Antigens, Humans, Male, Microglia, Middle Aged, Monocytes, Peptide Fragments, Plaque, Amyloid, Polymorphism, Genetic, Radionuclide Imaging, Sialic Acid Binding Ig-like Lectin 3, Thiazoles, Young Adult
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.

URLhttp://dx.doi.org/10.1038/nn.3435
DOI10.1038/nn.3435
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23708142?dopt=Abstract

Alternate JournalNat. Neurosci.
PubMed ID23708142
PubMed Central IDPMC3703870
Grant ListR01 AG17917 / AG / NIA NIH HHS / United States
K24 AG035007 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
K25 AG041906 / AG / NIA NIH HHS / United States
R01 AG030146 / AG / NIA NIH HHS / United States
P50 AG008702 / AG / NIA NIH HHS / United States
R01 AG043617 / AG / NIA NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
R10 NS067305 / NS / NINDS NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
P30 AG10161 / AG / NIA NIH HHS / United States
R01 NS067305 / NS / NINDS NIH HHS / United States
R25 GM076321 / GM / NIGMS NIH HHS / United States
R01 AG036042 / AG / NIA NIH HHS / United States
R01 AG11101 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
R01 AG15819 / AG / NIA NIH HHS / United States
RC2 GM093080 / GM / NIGMS NIH HHS / United States
P50 AG005138 / AG / NIA NIH HHS / United States
R01 AG30146 / AG / NIA NIH HHS / United States
R01 AG011101 / AG / NIA NIH HHS / United States
R01 AG031553 / AG / NIA NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States