Biomarkers of Neuroinflammation Proceedings of a Workshop (2018) / Chapter Skim
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4 Neuroinflammation in Disease
4 Neuroinflammation in Disease
Pages 25-36
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From page 25... ...
, even in mild cases, triggers a complex disease process involving both innate and adaptive immune responses, including neuroinflammation (Crawford)
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From page 26... ...
Bar-Or described a simplified immune pathogenesis model of MS in which immune cells in the periphery are activated, upregulating a series of molecules that enable the immune cells to more efficiently cross the blood‒brain barrier (BBB) , where they are reactivated.
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From page 27... ...
Histopathological studies have shown that immune cells accumulate at the meninges in individuals with MS, and of interest is whether they contribute to cortical injury. Within the cortext underlying such meningeal immune cell collections, there is evidence of neuronal injury and microglial activation.
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From page 28... ...
Crawford described the complex disease processes underlying both the acute injury and the secondary consequences of TBI, including calcium dysregulation, mitochondrial dysfunction, free radical generation, and neuroinflammation. Both innate and adaptive immune responses are
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From page 29... ...
For example, there are major differences in the brain architecture between mouse and human, and mice do not develop the hallmark pathology for CTE that is seen in humans -- deposition of tau in the depths of the sulci -- although she said that many other pathological features are similar across species. Crawford and colleagues have demonstrated in their mouse models similar axonal transport changes and axonal injury, accumulation of amyloid precursor protein (APP)
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From page 30... ...
repeats in the gene for huntingtin protein, said Stevens, noting that although the mutation occurs in all cells in the body, there is a selective vulnerability to neurodegeneration of the neural circuit between the motor cortex and striatum, and medium spiny neurons in the striatum. This regional and cellular specificity and the availability of several mouse models make HD a useful model to examine the mechanisms un
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From page 31... ...
These studies show that progressive synapse loss begins in a regionally specific manner in disease and in the absence of neuroinflammation. In animal models, they have been able to follow synapse loss over time, demonstrating that it begins early in the preclinical stages of disease, even before there is overt inflammation.
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From page 32... ...
For example, they show that brain amyloid is preceded by peripheral inflammation and low insulin signaling and that it coincides with low adiposity, low insulin signaling, and an anti-inflammatory milieu. Amyloidassociated dementia is also preceded by neuroinflammation as well as vasculopathy and BBB dysfunction and other hormonal and metabolic changes.
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From page 33... ...
Several studies have also provided evidence indicating that these markers of inflammation reflect causative mechanisms in depression, said Bullmore. For example, in a study conducted in a birth cohort population from Avon County, England, IL-6 and CRP levels obtained at 9
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From page 34... ...
. Similarly, Bullmore cited unpublished data from the MRC Consortium showing that elevated CRP levels in non-depressed women in 2004 and 2008 were associated with approximately a threefold increased risk of becoming depressed in 2012, compared to women with no evidence of inflammation.
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From page 35... ...
While CRP may not be the ideal biomarker, this study demonstrates the potential of biomarkers to improve clinical trials, said Bullmore. The need for better biomarkers prompted the development of BIODEP, a biomarker discovery program funded by the Wellcome Trust Consortium (see Chapter 7)
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