CD33 in Alzheimer's disease

Mol Neurobiol. 2014 Feb;49(1):529-35. doi: 10.1007/s12035-013-8536-1. Epub 2013 Aug 28.


The amyloid-beta peptide (Aβ) cascade hypothesis posits that Aβ accumulation is the fundamental initiator of Alzheimer's disease (AD), and mounting evidence suggests that impaired Aβ clearance rather than its overproduction is the major pathogenic event for AD. Recent genetic studies have identified cluster of differentiation 33 (CD33) as a strong genetic locus linked to AD. As a type I transmembrane protein, CD33 belongs to the sialic acid-binding immunoglobulin-like lectins, mediating the cell-cell interaction and inhibiting normal functions of immune cells. In the brain, CD33 is mainly expressed on microglial cells. The level of CD33 was found to be increased in the AD brain, which positively correlated with amyloid plaque burden and disease severity. More importantly, CD33 led to the impairment of microglia-mediated clearance of Aβ, which resulted in the formation of amyloid plaques in the brain. In this article, we review the recent epidemiological findings of CD33 that related with AD and discuss the levels and pathogenic roles of CD33 in this disease. Based on the contributing effects of CD33 in AD pathogenesis, targeting CD33 may provide new opportunities for AD therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Humans
  • Microglia / metabolism
  • Microglia / pathology
  • Plaque, Amyloid / genetics
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Polymorphism, Single Nucleotide / genetics
  • Sialic Acid Binding Ig-like Lectin 3 / genetics*
  • Sialic Acid Binding Ig-like Lectin 3 / metabolism*


  • CD33 protein, human
  • Sialic Acid Binding Ig-like Lectin 3