ArticleHuman molecular genetics2015
Tau deposition drives neuropathological, inflammatory and behavioral abnormalities independently of neuronal loss in a novel mouse model.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 79 citations in OpenAlex.
- Dorsal raphe tau pathology disrupts sleep-wake orchestration and sleep architecture in a sex-specific manner.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Amyloid exacerbates tau and alpha-synuclein pathologies, behavioral impairments, and neuroinflammation in a mixed dementia model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Phosphorylation at serine 214 correlates with tau seeding activity in an age-dependent manner in two mouse models for tauopathies and is required for tau transsynaptic propagation.Journal of Alzheimer's disease : JAD · 2025Article
- Article
- Distinct 11C-ER176 PET Neuroinflammatory Profiles and Tau Colocalization in Progressive Apraxia of Speech With and Without Parkinson-plus Syndrome.Clinical nuclear medicine · 2025Article
- Modeling Alzheimer's Disease: A Review of Gene-Modified and Induced Animal Models, Complex Cell Culture Models, and Computational Modeling.Brain sciences · 2025Review
- Chronic alcohol exposure during young adulthood attenuates microglial reactivity and downstream immune response pathways in a mouse model of tauopathy later in life.Alcohol, clinical & experimental research · 2025Article
- Towards realistic simulation of disease progression in the visual cortex with CNNs.Scientific reports · 2025Article
- Tau pathology in the dorsal raphe may be a prodromal indicator of Alzheimer's disease.Molecular psychiatry · 2025Article
- Advancing Alzheimer's research by improving disease modeling of secondary tauopathy.NPJ dementia · 2025Review
- Profiling the impact of different tau species on glial cell biology.Frontiers in cell and developmental biology · 2025Article
- Amyloid pathology and cognitive impairment in hAβ-KI and APPNeurobiology of aging · 2025Article
- AAV8-P301L tau expression confers age-related disruptions in sleep quantity and timing.Npj biological timing and sleep · 2024Article
- Targeted brain-specific tauopathy compromises peripheral skeletal muscle integrity and function.Aging brain · 2024Article
- Targeted brain-specific tauopathy compromises peripheral skeletal muscle integrity and function.bioRxiv : the preprint server for biology · 2023Article
- Network analysis identifies strain-dependent response to tau and tau seeding-associated genes.The Journal of experimental medicine · 2023Article
- Microglial REV-ERBα regulates inflammation and lipid droplet formation to drive tauopathy in male mice.Nature communications · 2023Article
- CRISPR interference to evaluate modifiers ofFrontiers in cell and developmental biology · 2023Article
- Influence of Host Age on Intracranial AAV9 TauP301L Induced Tauopathy.Journal of Alzheimer's disease : JAD · 2023Article
- Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer's disease.Molecular brain · 2022Article
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Aberrant tau protein accumulation drives neurofibrillary tangle (NFT) formation in several neurodegenerative diseases. Currently, efforts to elucidate pathogenic mechanisms and assess the efficacy of therapeutic targets are limited by constraints of existing models of tauopathy. In order to generate a more versatile mouse model of tauopathy, somatic brain transgenesis was utilized to deliver adeno-associated virus serotype 1 (AAV1) encoding human mutant P301L-tau compared with GFP control. At 6 months of age, we observed widespread human tau expression with concomitant accumulation of hyperphosphorylated and abnormally folded proteinase K resistant tau. However, no overt neuronal loss was observed, though significant abnormalities were noted in the postsynaptic scaffolding protein PSD95. Neurofibrillary pathology was also detected with Gallyas silver stain and Thioflavin-S, and electron microscopy revealed the deposition of closely packed filaments. In addition to classic markers of tauopathy, significant neuroinflammation and extensive gliosis were detected in AAV1-Tau(P301L) mice. This model also recapitulates the behavioral phenotype characteristic of mouse models of tauopathy, including abnormalities in exploration, anxiety, and learning and memory. These findings indicate that biochemical and neuropathological hallmarks of tauopathies are accurately conserved and are independent of cell death in this novel AAV-based model of tauopathy, which offers exceptional versatility and speed in comparison with existing transgenic models. Therefore, we anticipate this approach will facilitate the identification and validation of genetic modifiers of disease, as well as accelerate preclinical assessment of potential therapeutic targets.
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