Secretion of human tau fragments resembling CSF-tau in Alzheimer's disease is modulated by the presence of the exon 2 insert

FEBS Lett. 2010 Jul 16;584(14):3085-8. doi: 10.1016/j.febslet.2010.05.042. Epub 2010 May 27.

Abstract

Abnormal tau cleavage is prominent in the neurofibrillary degeneration characteristic of Alzheimer's disease (AD) and related tauopathies. We recently showed that cleaved human tau is secreted by specific mechanisms when overexpressed. Here we examined the effect of expressing N-terminal and full length tau constructs in transiently and stably transfected neuronal lines. We show that secreted tau exhibits a cleavage pattern similar to CSF-tau from human AD patients and that tau secretion is specifically inhibited by the presence of the exon 2 insert. These results suggest that tau secretion may play a hitherto unsuspected role in AD and related tauopathies.

MeSH terms

  • Alzheimer Disease / genetics
  • Animals
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / therapeutic use
  • Dosage Forms
  • Drug Administration Routes
  • Exons*
  • Humans
  • Mice
  • Neurofibrillary Tangles / genetics
  • Neurofibrillary Tangles / metabolism
  • Neurons / metabolism
  • Tauopathies / drug therapy
  • Tauopathies / genetics

Substances

  • Cytoskeletal Proteins
  • Dosage Forms