Premium
O1‐07‐03: Aggregation and size‐dependent uptake and transport of tau aggregates in neurons
Author(s) -
Wu Jessica,
Herman Mathieu,
Duff Karen
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.241
Subject(s) - fibril , tau protein , biophysics , chemistry , protein aggregation , microbiology and biotechnology , biochemistry , biology , alzheimer's disease , medicine , disease , pathology
but not GSK3̂I6, reduced BACE1-mediated cleavage of APP and Ab production by decreasing BACE1 gene transcription and expression. The regulation of BACE1 gene expression by GSK3b is dependent on NF̂IB signaling. Specific inhibition of GSK3 signaling markedly reduced Ab deposition and neuritic plaque formation, and rescued memory deficits in the double transgenic AD model mice. Taken together, our data provide evidence for regulation of BACE1 expression and AD pathogenesis by GSK3b and that inhibition of GSK3 signaling can reduce Ab neuropathology and alleviate memory deficits in AD model mice. Conclusions: Our study suggests that interventions that target the b-isoform of GSK3 specifically may be a safe and effective approach for treating AD.