Functional protection in J20/VLW mice: a model of non-demented with Alzheimer's disease neuropathology.

Alzheimer's disease comprises amyloid-β and hyperphosphorylated Tau accumulation, imbalanced neuronal activity, aberrant oscillatory rhythms and cognitive deficits. Non-demented with Alzheimer's disease neuropathology defines a novel clinical entity with amyloid-β and Tau pathologies but preserved cognition. The mechanisms underlying such neuroprotection remain undetermined and animal models of non-demented with Alzheimer's disease neuropathology are currently unavailable.

Differential accumulation of Tau phosphorylated at residues Thr231, Ser262 and Thr205 in hippocampal interneurons and its modulation by Tau mutations (VLW) and amyloid-β peptide.

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β peptide (Aβ) and hyperphosphorylated Tau protein (P-Tau). Our recent data showed a differential accumulation of Tau protein phosphorylated at residue Thr231 (pThr231) in distinct hippocampal neurons in VLW mice-a model that overexpresses mutated human Tau. Here we demonstrate that, in VLW mice, the accumulation of human P-Tau in pyramidal cells induces the phosphorylation of murine Tau at residue Thr231 in hippocampal interneurons.