Tau acts as a mediator for Alzheimer's disease-related synaptic deficits

Dezhi Liao, Eric C. Miller, Peter J. Teravskis

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The two histopathological hallmarks of Alzheimer's disease (AD) are amyloid plaques containing multiple forms of amyloid beta (Aβ) and neurofibrillary tangles containing phosphorylated tau proteins. As mild cognitive impairment frequently occurs long before the clinical diagnosis of AD, the scientific community has been increasingly interested in the roles of Aβ and tau in earlier cellular changes that lead to functional deficits. Therefore, great progress has recently been made in understanding how Aβ or tau causes synaptic dysfunction. However, the interaction between the Aβ and tau-initiated intracellular cascades that lead to synaptic dysfunction remains elusive. The cornerstone of the two-decade-old hypothetical amyloid cascade model is that amyloid pathologies precede tau pathologies. Although the premise of Aβ-tau pathway remains valid, the model keeps evolving as new signaling events are discovered that lead to functional deficits and neurodegeneration. Recent progress has been made in understanding Aβ-PrPC-Fyn-mediated neurotoxicity and synaptic deficits. Although still elusive, many novel upstream and downstream signaling molecules have been found to modulate tau mislocalization and tau hyperphosphorylation. Here we will discuss the mechanistic interactions between Aβ-PrPC-mediated neurotoxicity and tau-mediated synaptic deficits in an updated amyloid cascade model with calcium and tau as the central mediators.

Original languageEnglish (US)
Pages (from-to)1202-1213
Number of pages12
JournalEuropean Journal of Neuroscience
Volume39
Issue number7
DOIs
StatePublished - Apr 2014

Keywords

  • Amyloid beta
  • Amyloid cascade hypothesis
  • Dendritic spines
  • Soluble proteins
  • Synaptic dysfunction

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