Inflammatory pathology markers (activated microglia and reactive astrocytes) in early and late onset Alzheimer disease: a <i>post mortem</i> study

Taipa, Ricardo; Ferreira, Vanessa; Brochado, Paulo; Robinson, Andrew C; Reis, Isildinha; Marques, Fernanda; Mann, David; Pires, Manuel Melo; Sousa, Nuno

doi:10.1111/nan.12445

Cited by 59 publications

(55 citation statements)

References 56 publications

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“…Interestingly, some studies demonstrate that the antiinflammatory effect of exercise in AD was attributed to the clearance of amyloid plaques [23], the plaques being a trigger of inflammation. Activated microglia and reactive astrocytes are identified as inflammatory pathology markers in AD [33]. In this study, we showed a decrease in microglial activation in the frontal cortex and hippocampus after resistance training, accompanied by a decrease in the activation of astrocytes in the DG region of the hippocampus.…”

Section: Discussionsupporting

confidence: 58%

Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer’s disease mice

Liu

Chu

Yan

et al. 2020

J Neuroinflammation

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Background: Both human and animal studies have shown beneficial effects of physical exercise on brain health but most tend to be based on aerobic rather than resistance type regimes. Resistance exercise has the advantage of improving both muscular and cardiovascular function, both of which can benefit the frail and the elderly. However, the neuroprotective effects of resistance training in cognitive impairment are not well characterized. Methods: We evaluated whether short-term resistant training could improve cognitive function and pathological changes in mice with pre-existing cognitive impairment. Nine-month-old 3xTg mouse underwent a resistance training protocol of climbing up a 1-m ladder with a progressively heavier weight loading. Results: Compared with sedentary counterparts, resistance training improved cognitive performance and reduced neuropathological and neuroinflammatory changes in the frontal cortex and hippocampus of mice. In line with these results, inhibition of pro-inflammatory intracellular pathways was also demonstrated. Conclusions: Short-term resistance training improved cognitive function in 3xTg mice, and conferred beneficial effects on neuroinflammation, amyloid and tau pathology, as well as synaptic plasticity. Resistance training may represent an alternative exercise strategy for delaying disease progression in Alzheimer's disease.

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Section: Discussionsupporting

confidence: 58%

Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer’s disease mice

Liu

Chu

Yan

et al. 2020

J Neuroinflammation

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“…Their regional distribution follows that of the pathologic changes in AD. Recent studies indicate that the age of the individual also plays a role in microglial pathogenesis (63). The presence of microglia can be both detrimental and beneficial to AD pathogenesis.…”

Section: Microglia Heterogeneity and Admentioning

confidence: 99%

Unravelling the glial response in the pathogenesis of Alzheimer's disease

2018

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Alzheimer's disease is a progressive, incurable neurodegenerative disease targeting specific neuronal populations within the brain while neighboring neurons appear unaffected. The focus for defining mechanisms has therefore been on the pathogenesis in affected neuronal populations and developing intervention strategies to prevent their cell death. However, there is growing recognition of the importance of glial cells in the development of pathology. Determining exactly how glial cells are involved in the disease process and the susceptibility of the aging brain provides unprecedented challenges. The present review examines recent studies attempting to unravel the glial response during the course of disease and how this action may dictate the outcome of neurodegeneration. The importance of regional heterogeneity of glial cells within the CNS during healthy aging and disease is examined to understand how the glial cells may contribute to neuronal susceptibility or resilience during the neurodegenerative process.—Alibhai, J. D., Diack, A. B., Manson, J. C. Unravelling the glial response in the pathogenesis of Alzheimer's disease. 32, 5766–5777 (2018). http://www.fasebj.org

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“…40,41 Reassuringly, a recent postmortem investigation of microglial activation measured morphologically in the brains of 11 late onset AD subjects vs. 12 age-matched controls also found increases in microglial activation in cortical but not sub-cortical regions. 4 Second, we have a limited sample size for genome-wide analyses, although it was sufficient to discover the rs2997325 variant which has a strong effect on both microglial activation and in vivo imaging. Third, our moderate sample size also means that we cannot exclude that activated microglia may have weak, undetected effects on non-AD pathologies.…”

Section: Discussionmentioning

confidence: 99%

“…Recent postmortem studies have shown that microglial densities in specific regions are associated with a syndromic diagnosis of both early and late-onset AD, 4 and a recent systematic review of 113 studies quantifying microglial activation in postmortem AD brain highlighted the importance of activation vs. abundance of these cells in disease. 5 However, low sample sizes, indirect measures of microglia, and lack of full antemortem and postmortem pathological assessments all limit the insights that can be drawn from the component studies and this systematic review.…”

Section: Introductionmentioning

confidence: 99%

Neuropathological correlates and genetic architecture of microglial activation in elderly human brain

Felsky

Roostaei

Nho

et al. 2018

Preprint

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Microglia, the resident immune cells of the brain, have important roles in brain health. However, little is known about the regulation and consequences of microglial activation in the aging human brain. We assessed the effect of microglial activation in the aging human brain by calculating the proportion of activated microglia (PAM), based on morphologically defined stages of activation in four regions sampled postmortem from up to 225 elderly individuals. We found that cortical and not subcortical PAM measures were strongly associated with β-amyloid, tau-related neuropathology, and rates of cognitive decline. Effect sizes for PAM measures are substantial, comparable to that of APOE ε4, the strongest genetic risk factor for Alzheimer's disease.

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Inflammatory pathology markers (activated microglia and reactive astrocytes) in early and late onset Alzheimer disease: a post mortem study

Cited by 59 publications

References 56 publications

Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer’s disease mice

Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer’s disease mice

Unravelling the glial response in the pathogenesis of Alzheimer's disease

Neuropathological correlates and genetic architecture of microglial activation in elderly human brain

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