Adaptor protein interactions: modulators of amyloid precursor protein metabolism and Alzheimer's disease risk?

Exp Neurol. 2004 Feb;185(2):208-19. doi: 10.1016/j.expneurol.2003.10.011.


The cytoplasmic C-terminus of APP plays critical roles in its cellular trafficking and delivery to proteases. Adaptor proteins with phosphotyrosine-binding (PTB) domains, including those in the X11, Fe65, and c-Jun N-terminal kinase (JNK)-interacting protein (JIP) families, bind specifically to the absolutely conserved -YENPTY- motif in the APP C-terminus to regulate its trafficking and processing. Compounds that modulate APP-adaptor protein interactions may inhibit Abeta generation by specifically targeting the substrate (APP) instead of the enzyme (beta- or gamma-secretase). Genetic polymorphisms in (or near) adaptor proteins may influence risk of sporadic AD by interacting with APP in vivo to modulate its trafficking and processing to Abeta.

Publication types

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

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Adaptor Proteins, Vesicular Transport / physiology*
  • Alzheimer Disease / etiology
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Amino Acid Sequence
  • Amyloid beta-Protein Precursor / chemistry
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Humans
  • Molecular Sequence Data
  • Risk Factors


  • Adaptor Proteins, Vesicular Transport
  • Amyloid beta-Protein Precursor