Prevention of tau increase in cerebrospinal fluid of APP transgenic mice suggests downstream effect of BACE1 inhibition.
INTRODUCTION
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.
['Schelle|Juliane|J|', 'Häsler|Lisa M|LM|', 'Göpfert|Jens C|JC|', 'Joos|Thomas O|TO|', 'Vanderstichele|Hugo|H|', 'Stoops|Erik|E|', 'Mandelkow|Eva-Maria|EM|', 'Neumann|Ulf|U|', 'Shimshek|Derya R|DR|', 'Staufenbiel|Matthias|M|', 'Jucker|Mathias|M|', 'Kaeser|Stephan A|SA|']
D000375:Aging D000544:Alzheimer Disease D053829:Amyloid Precursor Protein Secretases D016229:Amyloid beta-Peptides D000818:Animals D016282:Aspartic Acid Endopeptidases D004195:Disease Models, Animal D004791:Enzyme Inhibitors D005260:Female D006801:Humans D007118:Immunoassay D008297:Male D008810:Mice, Inbred C57BL D008822:Mice, Transgenic D010848:Picolinic Acids D058225:Plaque, Amyloid D016548:Prosencephalon D013843:Thiazines D016875:tau Proteins
Tau Treatment Alzheimer's disease CSF BACE1 inhibitor Biomarker