Prevention of tau increase in cerebrospinal fluid of APP transgenic mice suggests downstream effect of BACE1 inhibition
Abstract
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Preclinical studies provide compelling evidence supporting early brain amyloidosis as a driver of tau hyperphosphorylation in AD.
“Preclinical studies provide compelling evidence supporting early brain amyloidosis as a driver of tau hyperphosphorylation in AD.14,15”
From Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer's disease (2022) · cites this paper as [15]
The findings challenge the purported roles of tau/p-tau in DIAD, and possibly AD generally, and reproduce in humans animal findings that link Aβ pathology to tau hyperphosphorylation and active cellular release rather than release from dying neurons.
“Moreover, they challenge the purported roles of tau/p-tau in DIAD, and possibly AD in general, and recapitulate in humans those findings from animal studies that link Aβ pathology to tau hyperphosphorylation32,34,36,49 and active cellular release, rather than release of dying neurons.”
From A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease (2020) · cites this paper as [34]
The citation lists haven’t been fetched yet
References 23 · Cited by 40
- Authors
- Schelle, J., Häsler, L. M., Göpfert, J. C., Joos, T. O., Vanderstichele, H., Stoops, E., Mandelkow, E., Neumann, U., Shimshek, D. R., Staufenbiel, M., Jucker, M., & Kaeser, S. A.
- Affiliations
- German Center for Neurodegenerative Diseases (DE)
- Natural and Medical Sciences Institute (DE)
- ADx NeuroSciences (BE)
- Center of Advanced European Studies and Research (DE)
- Novartis (Switzerland) (CH)
- Hertie Institute for Clinical Brain Research (DE)
- Corresponding author
- Jucker, Mathias
- Kaeser, Stephan A.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2016-10-14
- Volume
- 13
- Issue
- 6
- Pages
- 701-709
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2535103378
- Cited by
- 40
- References
- 23
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 2 · 2022: 10 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 2 · 2017: 2 · 2016: 1
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- DZNE Pub (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- BACE1 inhibition, tau protein
- MeSH terms
- Aging, Alzheimer Disease, Animals, Disease Models, Animal, Enzyme Inhibitors, Female, Humans, Immunoassay, Male, Mice, Inbred C57BL, Mice, Transgenic, Picolinic Acids, Thiazines, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Prosencephalon, tau Proteins, Amyloid Precursor Protein Secretases, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
