ArticleHuman molecular genetics2017
Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia.Brain communications · 2023Article
- Modelling amyotrophic lateral sclerosis in rodents.Nature reviews. Neuroscience · 2022Review
- Alteration of the Neuromuscular Junction and Modifications of Muscle Metabolism in Response to Neuron-Restricted Expression of the CHMP2BBiomolecules · 2022Article
- Review
- Replicative senescence dictates the emergence of disease-associated microglia and contributes to Aβ pathology.Cell reports · 2021Article
- Repetitive Traumatic Brain Injury Causes Neuroinflammation before Tau Pathology in Adolescent P301S Mice.International journal of molecular sciences · 2021Article
- Innate Immunity: A Common Denominator between Neurodegenerative and Neuropsychiatric Diseases.International journal of molecular sciences · 2020Review
- Cerebrospinal Fluid YKL-40 and Chitotriosidase Levels in Frontotemporal Dementia Vary by Clinical, Genetic and Pathological Subtype.Dementia and geriatric cognitive disorders · 2020Article
- CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice.Brain : a journal of neurology · 2019Article
- Neuroinflammation in frontotemporal dementia.Nature reviews. Neurology · 2019Review
- The pro-apoptotic JNK scaffold POSH/SH3RF1 mediates CHMP2BIntron5-associated toxicity in animal models of frontotemporal dementia.Human molecular genetics · 2018Article
- Article
- Dysregulated molecular pathways in amyotrophic lateral sclerosis-frontotemporal dementia spectrum disorder.The EMBO journal · 2017Review
- MicroRNA Profiling Reveals Marker of Motor Neuron Disease in ALS Models.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Endo-lysosomal protein concentrations in CSF from patients with frontotemporal dementia caused byAlzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD-like changes in social behaviour. These data are the first to show neurodegeneration in mice expressing mutant CHMP2B and indicate that our mouse model is able to recapitulate neurodegenerative changes observed in FTD. Neuroinflammation has been increasingly implicated in neurodegeneration, including FTD. Therefore, we investigated neuroinflammation in our CHMP2B mutant mice. We observed very early microglial proliferation that develops into a clear pro-inflammatory phenotype at late stages. Importantly, we also observed a similar inflammatory profile in CHMP2B patient frontal cortex. Aberrant microglial function has also been implicated in FTD caused by GRN, MAPT and C9orf72 mutations. The presence of early microglial changes in our CHMP2B mutant mice indicates neuroinflammation may be a contributing factor to the neurodegeneration observed in FTD.
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