Skip to Content
Merck
  • Expression of P301L-hTau in mouse MEC induces hippocampus-dependent memory deficit.

Expression of P301L-hTau in mouse MEC induces hippocampus-dependent memory deficit.

Scientific reports (2017-06-22)
Xinghua Liu, Kuan Zeng, Mengzhu Li, Qun Wang, Rong Liu, Bin Zhang, Jian-Zhi Wang, Xiji Shu, Xiaochuan Wang
ABSTRACT

Intracellular accumulation of abnormally phosphorylated tau in different types of neurons is a pathological characteristic of Alzheimer's disease (AD). While tau modification and associated neuronal loss and hypometabolism start in the entorhinal cortex (EC) in early AD patients, the mechanism by which mutant P301L hTau leads to dementia is not fully elucidated. Here, we studied the effects of P301L hTau transduction in the medial EC (MEC) of mice on tau phosphorylation and accumulation, and cognitive deficit. We found that the exogenous mutant tau protein was restricted in MEC without spreading to other brain regions at one month after transduction. Interestingly, expression of the mutant tau in MEC induces endogenous tau hyperphosphorylation and accumulation in hippocampus and cortex, and inhibits neuronal activity with attenuated PP-DG synapse plasticity, leading to hippocampus-dependent memory deficit with intact olfactory function. These findings suggest a novel neuropathological mechanism of early AD, which is initiated by tau accumulation in MEC, and demonstrate a tau pathological model of early stage AD.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-α-Tubulin antibody produced in mouse, clone DM1A, ascites fluid
Sigma-Aldrich
Anti-NMDAR1 Antibody, rabbit monoclonal, culture supernatant, clone 1.17.2.6, Chemicon®
Sigma-Aldrich
Anti-Tau Antibody, a.a. 210-241, clone Tau-5, ascites fluid, clone Tau-5, Chemicon®
Sigma-Aldrich
Anti-GluR1 Antibody, clone C3T, rabbit monoclonal, culture supernatant, clone C3T, Upstate®
Sigma-Aldrich
Anti-Tau phospho Serine 199 Antibody, Chemicon®, from rabbit