ArticlePloS one2018
Early intervention of tau pathology prevents behavioral changes in the rTg4510 mouse model of tauopathy.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Neurodevelopmental Clues to Neurodegeneration.Pediatric neurology · 2021Pooled it
- Results of the first-in-human, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study of BIIB113 in healthy volunteers.The journal of prevention of Alzheimer's disease · 2025Trial
- Diet-Dependent Cognitive Benefits of Exogenous Ketone Body Precursor, (R,S)-1,3,-Butanediol, in a Mouse Model of Tauopathy.bioRxiv : the preprint server for biology · 2026Article
- Discovery of 5‑Azaindole Inhibitors of O‑GlcNAcase for the Treatment of Alzheimer's Disease and Related Tauopathies.ACS medicinal chemistry letters · 2026Article
- Hippocampus-targeted BDNF gene therapy to rescue cognitive impairments of Alzheimer's disease in multiple mouse models.Genes & diseases · 2026Article
- Aquaporin dysfunction and impaired brain interstitial fluid clearance in Alzheimer's disease - an integrative review.Frontiers in cellular neuroscience · 2026Review
- Twenty years of therapeutic development in tauopathy mouse models: a scoping review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- An Efficient and Accessible Hectogram-Scale Synthesis for the Selective O-GlcNAcase Inhibitor Thiamet-G.ACS omega · 2024Article
- O-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations.Nature communications · 2023Article
- Chemical Biology Approaches to Understanding Neuronal O-GlcNAcylation.Israel journal of chemistry · 2023Article
- Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer's disease.Molecular brain · 2022Article
- Small Heat Shock Protein 22 Improves Cognition and Learning in the Tauopathic Brain.International journal of molecular sciences · 2022Article
- Consequences of Hyperphosphorylated Tau in the Locus Coeruleus on Behavior and Cognition in a Rat Model of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2022Article
- Recent advances on drug development and emerging therapeutic agents for Alzheimer's disease.Molecular biology reports · 2021Review
- Severe oligomeric tau toxicity can be reversed without long-term sequelae.Brain : a journal of neurology · 2021Article
- New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2020Article
- Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of Tauopathy.Frontiers in molecular neuroscience · 2020Article
- A walk through tau therapeutic strategies.Acta neuropathologica communications · 2019Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although tau pathology, behavioral deficits, and neuronal loss are observed in patients with tauopathies, the relationship between these endpoints has not been clearly established. Here we found that rTg4510 mice, which overexpress human mutant tau in the forebrain, develop progressive age-dependent increases in locomotor activity (LMA), which correlates with neurofibrillary tangle (NFT) pathology, hyperphosphorylated tau levels, and brain atrophy. To further clarify the relationship between these endpoints, we treated the rTg4510 mice with either doxycycline to reduce mutant tau expression or an O-GlcNAcase inhibitor Thiamet G, which has been shown to ameliorate tau pathology in animal models. We found that both doxycycline and Thiamet G treatments starting at 2 months of age prevented the progression of hyperactivity, slowed brain atrophy, and reduced brain hyperphosphorylated tau. In contrast, initiating doxycycline treatment at 4 months reduced neither brain hyperphosphorylated tau nor hyperactivity, further confirming the relationship between these measures. Collectively, our results demonstrate a unique behavioral phenotype in the rTg4510 mouse model of tauopathy that strongly correlates with disease progression, and that early interventions which reduce tau pathology ameliorate the progression of the locomotor dysfunction. These findings suggest that better understanding the relationship between locomotor deficits and tau pathology in the rTg4510 model may improve our understanding of the mechanisms underlying behavioral disturbances in patients with tauopathies.
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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.