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Prevention of tau increase in cerebrospinal fluid of APP transgenic mice suggests downstream effect of BACE1 inhibition

Schelle, Juliane and Häsler, Lisa and Göpfert, Jens C and Joos, Thomas O and Vanderstichele, Hugo and Stoops, Erik and Neumann, Ulf and Shimshek, Derya and Staufenbiel, Matthias and Jucker, Mathias and Kaeser, Stephan A (2016) Prevention of tau increase in cerebrospinal fluid of APP transgenic mice suggests downstream effect of BACE1 inhibition. Alzheimer's & dementia. ISSN 15525260

Abstract

The inhibition of the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is a main therapeutic approach for the treatment of Alzheimer's disease (AD). The characterization of BACE1 inhibitors has largely focused on direct effects, i.e. the reduction of β-amyloid (Aβ) generation and deposition in the brain. We reported previously the age-related increase of tau protein in the cerebrospinal fluid (CSF) of Aβ precursor protein (APP) transgenic mice reminiscent of similar changes in AD CSF. Using a novel high-sensitivity tau sandwich immunoassay we now demonstrate that BACE1 inhibition prevents CSF tau increase in both, early-depositing APP tg mice and mice with moderate Aβ pathology. Our results demonstrate that BACE1 inhibition not only reduces Aβ generation but also downstream AD pathologies. The tight correlation between Aβ aggregation in brain and tau levels in CSF renders CSF tau a valuable marker to predict the effectiveness of BACE inhibitors in current clinical trials.

Item Type: Article
Date Deposited: 26 Apr 2017 00:45
Last Modified: 26 Apr 2017 00:45
URI: https://oak.novartis.com/id/eprint/29200

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