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

Autor:	Hugo Vanderstichele, Derya R. Shimshek, Stephan A. Kaeser, Mathias Jucker, Juliane Schelle, Jens C. Göpfert, Matthias Staufenbiel, Erik Stoops, Eva-Maria Mandelkow, Lisa M. Häsler, Thomas O. Joos, Ulf Neumann
Jazyk:	angličtina
Rok vydání:	2017
Předmět:	0301 basic medicine Male Aging Epidemiology drug effects [Prosencephalon] Thiazines pharmacology [Enzyme Inhibitors] Plaque Amyloid antagonists & inhibitors [Amyloid Precursor Protein Secretases] cerebrospinal fluid [Amyloid beta-Peptides] Pharmacology pathology [Alzheimer Disease] 0302 clinical medicine Cerebrospinal fluid pathology [Prosencephalon] pharmacology [Thiazines] drug therapy [Plaque Amyloid] drug therapy [Alzheimer Disease] Aspartic Acid Endopeptidases Sandwich immunoassay Enzyme Inhibitors Picolinic Acids chemistry.chemical_classification Immunoassay biology metabolism [Prosencephalon] Chemistry Health Policy antagonists & inhibitors [Aspartic Acid Endopeptidases] Pathophysiology drug effects [Aging] Psychiatry and Mental health pharmacology [Picolinic Acids] Biomarker (medicine) Female metabolism [Alzheimer Disease] Mapt protein mouse Genetically modified mouse Amyloid Bace1 protein mouse Tau protein Mice Transgenic tau Proteins 03 medical and health sciences Cellular and Molecular Neuroscience Prosencephalon Developmental Neuroscience Alzheimer Disease mental disorders Animals Humans ddc:610 metabolism [Aging] pathology [Plaque Amyloid] Amyloid beta-Peptides metabolism [Plaque Amyloid] Mice Inbred C57BL Disease Models Animal 030104 developmental biology Enzyme cerebrospinal fluid [tau Proteins] NB-360 Immunology biology.protein Neurology (clinical) Geriatrics and Gerontology Amyloid Precursor Protein Secretases 030217 neurology & neurosurgery
Zdroj:	Alzheimer's and dementia 13(6), 701-709 (2017). doi:10.1016/j.jalz.2016.09.005 Alzheimer's and Dementia
DOI:	10.1016/j.jalz.2016.09.005
Popis:	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.
Databáze:	OpenAIRE
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