ArticleThe Journal of experimental medicine2019
rAAV-based brain slice culture models of Alzheimer's and Parkinson's disease inclusion pathologies.
Article in The Journal of experimental medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- Temporal Trajectories of the Tau Aggregate Interactome Reveal Stage-Specific Vulnerabilities in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Modeling Tau-Mediated Pathology in Monkey Brain Slices.Biology · 2026Article
- Human brain slice cultures: translational applications and ethical considerations.Life science alliance · 2025Review
- Dynein-Dependent Endo-Lysosomal Degradation Drives Lewy Body Disorders Accompanied by Aβ Pathology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Distinct patterns of prion strain deposition and toxicity in a novel whole brain organotypic slice culture system.Scientific reports · 2025Article
- Prion and "Prion-Like" Detection: From Conventional Methods to Microfluidics or Lab-on-Chip Platforms to Monitor Seeding and Spreading of Misfolded Proteins.Sub-cellular biochemistry · 2025Review
- DLK-MAPK Signaling Coupled with DNA Damage Promotes Intrinsic Neurotoxicity Associated with Non-Mutated Tau.Molecular neurobiology · 2024Article
- Reactive astrocytes secrete the chaperone HSPB1 to mediate neuroprotection.Science advances · 2024Article
- Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model.World journal of gastroenterology · 2024Article
- A Combination of Heavy Metals and Intracellular Pathway Modulators Induces Alzheimer Disease-like Pathologies in Organotypic Brain Slices.Biomolecules · 2024Article
- ContourTL-Net: Contour-Based Transfer Learning Algorithm for Early-Stage Brain Tumor Detection.International journal of biomedical imaging · 2024Article
- P2XBrain, behavior, and immunity · 2023Article
- Structurally and Morphologically Distinct Pathological Tau Assemblies Differentially Affect GVB Accumulation.International journal of molecular sciences · 2023Article
- Intraneuronal tau aggregation induces the integrated stress response in astrocytes.Journal of molecular cell biology · 2023Article
- A 3D human co-culture to model neuron-astrocyte interactions in tauopathies.Biological procedures online · 2023Article
- Optical pulse labeling studies reveal exogenous seeding slows α-synuclein clearance.NPJ Parkinson's disease · 2022Article
- Granulovacuolar degeneration bodies are independently induced by tau and α-synuclein pathology.Alzheimer's research & therapy · 2022Article
- Nuclear import receptors are recruited by FG-nucleoporins to rescue hallmarks of TDP-43 proteinopathy.Molecular neurodegeneration · 2022Article
- Advances in Understanding Neuropathogenesis of Rift Valley Fever Virus.Annual review of virology · 2022Review
- Pathogenic tau recruits wild-type tau into brain inclusions and induces gut degeneration in transgenic SPAM mice.Communications biology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
It has been challenging to produce ex vivo models of the inclusion pathologies that are hallmark pathologies of many neurodegenerative diseases. Using three-dimensional mouse brain slice cultures (BSCs), we have developed a paradigm that rapidly and robustly recapitulates mature neurofibrillary inclusion and Lewy body formation found in Alzheimer's and Parkinson's disease, respectively. This was achieved by transducing the BSCs with recombinant adeno-associated viruses (rAAVs) that express α-synuclein or variants of tau. Notably, the tauopathy BSC model enables screening of small molecule therapeutics and tracking of neurodegeneration. More generally, the rAAV BSC "toolkit" enables efficient transduction and transgene expression from neurons, microglia, astrocytes, and oligodendrocytes, alone or in combination, with transgene expression lasting for many months. These rAAV-based BSC models provide a cost-effective and facile alternative to in vivo studies, and in the future can become a widely adopted methodology to explore physiological and pathological mechanisms related to brain function and dysfunction.
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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.