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

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.