Neuropathological changes and cognitive deficits in rats transgenic for human mutant tau recapitulate human tauopathy

Malcolm, Janice C.; Breuillaud, Lionel; Carmo, Sonia Do; Hall, Hélène; Welikovitch, Lindsay A.; Macdonald, Jennifer A.; Goedert, Michel; Cuello, A. Claudio

doi:10.1016/j.nbd.2019.03.018

Cited by 18 publications

(6 citation statements)

References 59 publications

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“…Moreover, rod-like microglial cells might align to p-tau positive neurons in the DS frontal cortex (Flores-Aguilar et al, 2020 ). Rod-like microglial cells have been observed in other neurodegenerative disorders such as AD (Bachstetter et al, 2015 ) and might be linked to the appearance of tau pathology (Adaikkan et al, 2019 ; Malcolm et al, 2019 ). However, their exact function is not well-understood (Giordano et al, 2021 ).…”

Section: Microglia and Alzheimer's Disease In Down Syndromementioning

confidence: 99%

Astroglial and microglial pathology in Down syndrome: Focus on Alzheimer's disease

García

Aguilar²

2022

Front. Cell. Neurosci.

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Down syndrome (DS) arises from the triplication of human chromosome 21 and is considered the most common genetic cause of intellectual disability. Glial cells, specifically astroglia and microglia, display pathological alterations that might contribute to DS neuropathological alterations. Further, in middle adulthood, people with DS develop clinical symptoms associated with premature aging and Alzheimer's disease (AD). Overexpression of the amyloid precursor protein (APP) gene, encoded on chromosome 21, leads to increased amyloid-β (Aβ) levels and subsequent formation of Aβ plaques in the brains of individuals with DS. Amyloid-β deposition might contribute to astroglial and microglial reactivity, leading to neurotoxic effects and elevated secretion of inflammatory mediators. This review discusses evidence of astroglial and microglial alterations that might be associated with the AD continuum in DS.

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Section: Microglia and Alzheimer's Disease In Down Syndromementioning

confidence: 99%

Astroglial and microglial pathology in Down syndrome: Focus on Alzheimer's disease

García

Aguilar²

2022

Front. Cell. Neurosci.

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“…In the context of tau pathology, our results demonstrate the presence of rod microglia in the cortex of the P301S mouse. Other authors also reported that this microglia variant was present in tauopathy murine models such as Tx5 mouse (5xfAD crossed with Thy-Tau22) 63 and R926-hTau rat 64 . In addition to this, it has been shown that tau inoculation in the brain of mice caused the appearance of rod microglia, which was in the vicinity of AT8 + neurons [65][66][67] .…”

Section: Discussionmentioning

confidence: 84%

p38 activation occurs mainly in microglia in the P301S Tauopathy mouse model

Perea

García

Vallés-Saiz

et al. 2022

Sci Rep

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Tauopathies are a group of neurodegenerative diseases characterized by the accumulation of hyperphosphorylated tau protein in the brain. Many of these pathologies also present an inflammatory component determined by the activation of microglia, the resident immune cells of the brain. p38 MAPK is one of the molecular pathways involved in neuroinflammation. Although this kinase is expressed mainly in glia, its activation in certain neurodegenerative diseases such as Alzheimer's Disease has been associated with its ability to phosphorylate tau in neurons. Using the P301S Tauopathy mouse model, here we show that p38 activation increases during aging and that this occurs mainly in microglia of the hippocampus rather than in neurons. Furthermore, we have observed that these mice present an activated microglial variant called rod microglia. Interestingly, p38 activation in this subpopulation of microglia is decreased. On the basis of our findings, we propose that rod microglia might have a neuroprotective phenotype in the context of tau pathology.

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“…In rTg21221 mice that overproduced non-aggregating wild-type human tau but lacked neurofibrillary tangle accumulation, mainly ventricle enlargement was observed compared with wild-type mice (Wegmann et al, 2015;Musi et al, 2018). Malcolm et al (2019) characterized recently developed R962-hTau rats and reported ventricular dilation and hippocampal atrophy in this model.…”

Section: Arterial Spin Labelingmentioning

confidence: 97%

Magnetic Resonance Imaging in Tauopathy Animal Models

2022

Front. Aging Neurosci.

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The microtubule-associated protein tau plays an important role in tauopathic diseases such as Alzheimer’s disease and primary tauopathies such as progressive supranuclear palsy and corticobasal degeneration. Tauopathy animal models, such as transgenic, knock-in mouse and rat models, recapitulating tauopathy have facilitated the understanding of disease mechanisms. Aberrant accumulation of hyperphosphorylated tau contributes to synaptic deficits, neuroinflammation, and neurodegeneration, leading to cognitive impairment in animal models. Recent advances in molecular imaging using positron emission tomography (PET) and magnetic resonance imaging (MRI) have provided valuable insights into the time course of disease pathophysiology in tauopathy animal models. High-field MRI has been applied for in vivo imaging in animal models of tauopathy, including diffusion tensor imaging for white matter integrity, arterial spin labeling for cerebral blood flow, resting-state functional MRI for functional connectivity, volumetric MRI for neurodegeneration, and MR spectroscopy. In addition, MR contrast agents for non-invasive imaging of tau have been developed recently. Many preclinical MRI indicators offer excellent translational value and provide a blueprint for clinical MRI in the brains of patients with tauopathies. In this review, we summarized the recent advances in using MRI to visualize the pathophysiology of tauopathy in small animals. We discussed the outstanding challenges in brain imaging using MRI in small animals and propose a future outlook for visualizing tau-related alterations in the brains of animal models.

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Neuropathological changes and cognitive deficits in rats transgenic for human mutant tau recapitulate human tauopathy

Cited by 18 publications

References 59 publications

Astroglial and microglial pathology in Down syndrome: Focus on Alzheimer's disease

Astroglial and microglial pathology in Down syndrome: Focus on Alzheimer's disease

p38 activation occurs mainly in microglia in the P301S Tauopathy mouse model

Magnetic Resonance Imaging in Tauopathy Animal Models

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