Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms

TLDR

Neurofibrillary tangles are insoluble aggregates of tau, and in Alzheimer’s disease they accumulate without tau mutations. The study aims to develop a mouse model that develops Alzheimer‑like tau pathology from non‑mutant human tau alone. The model expresses normal human tau without other exogenous factors, including β‑amyloid, to induce this pathology. The mice display Alzheimer‑like pathology with hyperphosphorylated tau forming paired helical filaments that accumulate in neuronal cell bodies and dendrites in a spatiotemporally relevant distribution.

Abstract

Abstract Neurofibrillary tangles are composed of insoluble aggregates of the microtubule‐associated protein tau. In Alzheimer's disease the accumulation of neurofibrillary tangles occurs in the absence of tau mutations. Here we present mice that develop pathology from non‐mutant human tau, in the absence of other exogenous factors, including β‐amyloid. The pathology in these mice is Alzheimer‐like, with hyperphosphorylated tau accumulating as aggregated paired helical filaments. This pathologic tau accumulates in the cell bodies and dendrites of neurons in a spatiotemporally relevant distribution.