Membrane rafts in Alzheimer's disease beta-amyloid production

Biochim Biophys Acta. 2010 Aug;1801(8):860-7. doi: 10.1016/j.bbalip.2010.03.007. Epub 2010 Mar 18.


Alzheimer's disease (AD), the most common age-associated dementing disorder, is pathologically manifested by progressive cognitive dysfunction concomitant with the accumulation of senile plaques consisting of amyloid-beta (Abeta) peptide aggregates in the brain of affected individuals. Abeta is derived from a type I transmembrane protein, amyloid precursor protein (APP), by the sequential proteolytic events mediated by beta-site APP cleaving enzyme 1 (BACE1) and gamma-secretase. Multiple lines of evidence have implicated cholesterol and cholesterol-rich membrane microdomains, termed lipid rafts in the amyloidogenic processing of APP. In this review, we summarize the cell biology of APP, beta- and gamma-secretases and the data on their association with lipid rafts. Then, we will discuss potential raft targeting signals identified in the secretases and their importance on amyloidogenic processing of APP.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid Precursor Protein Secretases / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Cell Biology
  • Humans
  • Membrane Microdomains / metabolism
  • Membrane Microdomains / physiology*
  • Models, Biological
  • Protein Processing, Post-Translational / physiology


  • Amyloid beta-Peptides
  • Amyloid Precursor Protein Secretases