ALZHEIMER’S & DEMENTIA

Juliane Schelle et. al.
Alzheimer’s & Dementia 

Abstract

Introduction: 

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). We previously reported an age-related increase of tau protein in the cerebrospinal fluid (CSF) of 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 reduces not only 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 BACE inhibitors in current clinical trials.