ArticleMolecular neurodegeneration2014
Tau deletion impairs intracellular β-amyloid-42 clearance and leads to more extracellular plaque deposition in gene transfer models.
Article in Molecular neurodegeneration, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Open Label Study for the Use of Tyrosine Kinase Inhibitors for Treatment of Cognitive Decline Due to Degenerative Dementias
Anti-Inflammatory, Insulin-Sensitizing Agent for Treatment of Cognitive Decline Due to Degenerative Dementias
Who cites it
22 citing papers in PubMed, 50 citations in OpenAlex.
- Long-Term Safety and Clinical Effects of Nilotinib in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2021Trial
- Pharmacokinetics and pharmacodynamics of a single dose Nilotinib in individuals with Parkinson's disease.Pharmacology research & perspectives · 2019Trial
- Nilotinib Effects in Parkinson's disease and Dementia with Lewy bodies.Journal of Parkinson's disease · 2016Trial
- Spatial transcriptomics reveals an unexpected impact of tau and tau pathology on the expression of transthyretin.Frontiers in aging neuroscience · 2025Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Retraction: Ubiquitination increases Parkin activity to promote Autophagic α-Synuclein Clearance.PloS one · 2025Article
- Nilotinib as a Prospective Treatment for Alzheimer's Disease: Effect on Proteins Involved in Neurodegeneration and Neuronal Homeostasis.Life (Basel, Switzerland) · 2024Article
- A nonhuman primate model with Alzheimer's disease-like pathology induced by hippocampal overexpression of human tau.Alzheimer's research & therapy · 2024Article
- Inhibition of discoidin domain receptor (DDR)-1 with nilotinib alters CSF miRNAs and is associated with reduced inflammation and vascular fibrosis in Alzheimer's disease.Journal of neuroinflammation · 2023Article
- Circular RNAs: New players involved in the regulation of cognition and cognitive diseases.Frontiers in neuroscience · 2023Review
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Amyloid Cascade Hypothesis for the Treatment of Alzheimer's Disease: Progress and Challenges.Aging and disease · 2022Article
- Safety, target engagement, and biomarker effects of bosutinib in dementia with Lewy bodies.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- Treatment of Dementia With Bosutinib: An Open-Label Study of a Tyrosine Kinase Inhibitor.Neurology. Clinical practice · 2021Article
- Nilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer's Disease.Annals of neurology · 2020Article
- Exploring the bi-directional relationship between autophagy and Alzheimer's disease.CNS neuroscience & therapeutics · 2020Review
- Sulforaphane metabolites inhibit migration and invasion via microtubule-mediated Claudins dysfunction or inhibition of autolysosome formation in human non-small cell lung cancer cells.Cell death & disease · 2019Article
- Prospects for strain-specific immunotherapy in Alzheimer's disease and tauopathies.NPJ vaccines · 2018Review
- Two novel blood-based biomarker candidates measuring degradation of tau are associated with dementia: A prospective study.PloS one · 2018Observational
- Pazopanib Reduces Phosphorylated Tau Levels and Alters Astrocytes in a Mouse Model of Tauopathy.Journal of Alzheimer's disease : JAD · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTau is an axonal protein that binds to and regulates microtubule function. Hyper-phosphorylation of Tau reduces its binding to microtubules and it is associated with β-amyloid deposition in Alzheimer's disease. Paradoxically, Tau reduction may prevent β-amyloid pathology, raising the possibility that Tau mediates intracellular Aβ clearance. The current studies investigated the role of Tau in autophagic and proteasomal intracellular Aβ1-42 clearance and the subsequent effect on plaque deposition.
resultsTau deletion impaired Aβ clearance via autophagy, but not the proteasome, while introduction of wild type human Tau into Tau-/- mice partially restored autophagic clearance of Aβ1-42, suggesting that exogenous Tau expression can support autophagic Aβ1-42 clearance. Tau deletion impaired autophagic flux and resulted in Aβ1-42 accumulation in pre-lysosomal autophagic vacuoles, affecting Aβ1-42 deposition into the lysosome. This autophagic defect was associated with decreased intracellular Aβ1-42 and increased plaque load in Tau-/- mice, which displayed less cell death. Nilotinib, an Abl tyrosine kinase inhibitor that promotes autophagic clearance mechanisms, reduced Aβ1-42 only when exogenous human Tau was expressed in Tau-/- mice.
conclusionsThese studies demonstrate that Tau deletion affects intracellular Aβ1-42 clearance, leading to extracellular plaque.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.