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Prevention of tau increase in cerebrospinal fluid of APP transgenic mice suggests downstream effect of BACE1 inhibition
Author(s) -
Schelle Juliane,
Häsler Lisa M.,
Göpfert Jens C.,
Joos Thomas O.,
Vanderstichele Hugo,
Stoops Erik,
Mandelkow EvaMaria,
Neumann Ulf,
Shimshek Derya R.,
Staufenbiel Matthias,
Jucker Mathias,
Kaeser Stephan A.
Publication year - 2017
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.2016.09.005
Subject(s) - genetically modified mouse , cerebrospinal fluid , amyloid precursor protein , transgene , tau protein , chemistry , amyloid precursor protein secretase , amyloid (mycology) , microbiology and biotechnology , alzheimer's disease , endocrinology , medicine , disease , pathology , biology , biochemistry , gene
The inhibition of the β‐site amyloid precursor protein‐cleaving enzyme 1 (BACE1) is a main therapeutic approach for the treatment of Alzheimer's disease (AD). We previously reported an age‐related increase of tau protein in the cerebrospinal fluid (CSF) of amyloid β (Aβ) precursor protein (APP) transgenic mice. Methods APP transgenic mice were treated with a potent BACE1 inhibitor. CSF tau and CSF Aβ levels were assessed. A novel high‐sensitivity tau sandwich immunoassay was developed. Results We demonstrate that long‐term BACE1 inhibition prevents CSF tau increase both in early‐depositing APP transgenic mice and APP transgenic mice with moderate Aβ pathology. Discussion Our results demonstrate that BACE1 inhibition not only reduces Aβ generation but also downstream AD pathophysiology. The tight correlation between Aβ aggregation in brain and CSF tau levels renders CSF tau a valuable marker to predict the effectiveness of BACE1 inhibitors in current clinical trials.