The neuritic plaque facilitates pathological conversion of tau in an Alzheimer's disease mouse model

Tong Li, Kerstin E. Braunstein, Juhong Zhang, Ashley Lau, Leslie Sibener, Christopher Deeble, Philip Chun Wong

Research output: Contribution to journalArticle

Abstract

A central question in Alzheimer's Disease (AD) is whether the neuritic plaque is necessary and sufficient for the development of tau pathology. Hyperphosphorylation of tau is found within dystrophic neurites surrounding β-amyloid deposits in AD mouse models but the pathological conversion of tau is absent. Likewise, expression of a human tau repeat domain in mice is insufficient to drive the pathological conversion of tau. Here we developed an Aβ-amyloidosis mouse model that expresses the human tau repeat domain and show that in these mice, the neuritic plaque facilitates the pathological conversion of wild-type tau. We show that this tau fragment seeds the neuritic plaque-dependent pathological conversion of wild-type tau that spreads from the cortex and hippocampus to the brain stem. These results establish that in addition to the neuritic plaque, a second determinant is required to drive the conversion of wild-type tau.

Original languageEnglish (US)
Article number12082
JournalNature Communications
Volume7
DOIs
StatePublished - Jul 4 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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