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

Nat Neurosci. 2013 Jul;16(7):848-50. doi: 10.1038/nn.3435. Epub 2013 May 23.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Brain / diagnostic imaging
  • Brain / pathology
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / pathology
  • Cohort Studies
  • Dextrans / metabolism
  • Female
  • Genetic Association Studies
  • Genotype
  • HLA-D Antigens / metabolism
  • Humans
  • Male
  • Microglia / pathology
  • Middle Aged
  • Monocytes / metabolism*
  • Peptide Fragments / metabolism*
  • Plaque, Amyloid / pathology
  • Polymorphism, Genetic / genetics
  • Radionuclide Imaging
  • Sialic Acid Binding Ig-like Lectin 3 / genetics
  • Sialic Acid Binding Ig-like Lectin 3 / metabolism*
  • Thiazoles
  • Young Adult

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Dextrans
  • HLA-D Antigens
  • Peptide Fragments
  • Sialic Acid Binding Ig-like Lectin 3
  • Thiazoles
  • amyloid beta-protein (1-42)