N-terminal tau truncation in the pathogenesis of Alzheimer's disease (AD): Developing a novel diagnostic and therapeutic approach

Biochim Biophys Acta Mol Basis Dis. 2020 Mar 1;1866(3):165584. doi: 10.1016/j.bbadis.2019.165584. Epub 2019 Oct 29.

Abstract

Tau truncation occurs at early stages during the development of human Alzheimer's disease (AD) and other tauopathy dementias. Tau cleavage, particularly in its N-terminal projection domain, is able to drive per se neurodegeneration, regardless of its pro-aggregative pathway(s) and in fragment(s)-dependent way. In this short review, we highlight the pathological relevance of the 20-22 kDa NH2-truncated tau fragment which is endowed with potent neurotoxic "gain-of-function" action(s), both in vitro and in vivo. An extensive comment on its clinical value as novel progression/diagnostic biomarker and potential therapeutic target in the context of tau-mediated neurodegeneration is also provided.

Keywords: Alzheimer's disease (AD); Neurodegeneration; Synapse(s); Tau truncation; Tauopathies.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Animals
  • Biomarkers / metabolism
  • Disease Progression
  • Humans
  • Neurons / metabolism
  • Neurons / pathology
  • Tauopathies / metabolism
  • Tauopathies / pathology
  • tau Proteins / metabolism*

Substances

  • Biomarkers
  • tau Proteins