Tau reduction prevents Abeta-induced defects in axonal transport

Science. 2010 Oct 8;330(6001):198. doi: 10.1126/science.1194653. Epub 2010 Sep 9.

Abstract

Amyloid-β (Aβ) peptides, derived from the amyloid precursor protein, and the microtubule-associated protein tau are key pathogenic factors in Alzheimer's disease (AD). How exactly they impair cognitive functions is unknown. We assessed the effects of Aβ and tau on axonal transport of mitochondria and the neurotrophin receptor TrkA, cargoes that are critical for neuronal function and survival and whose distributions are altered in AD. Aβ oligomers rapidly inhibited axonal transport of these cargoes in wild-type neurons. Lowering tau levels prevented these defects without affecting baseline axonal transport. Thus, Aβ requires tau to impair axonal transport, and tau reduction protects against Aβ-induced axonal transport defects.

Publication types

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

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Axonal Transport*
  • Cells, Cultured
  • Hippocampus / cytology
  • Mice
  • Mitochondria / metabolism
  • Neurons / metabolism*
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Receptor, trkA / metabolism
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Receptor, trkA