Identifying Neuroimaging Markers of Neuroinflammation in Neurodegenerative Diseases

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Immune-responsive cells of the brain – namely microglia and astrocytes – activate in response to brain injury or pathogens. This activation leads to a local neuroinflammatory response that serves to isolate and protect the tissue, remove the noxious agent, and promote recovery. However, while beneficial in the short term, the chronic release of pro-inflammatory chemicals (cytokines and chemokines) becomes increasingly toxic, and actually begins to contribute to neuropathology in its own right. Chronic neuroinflammation is thought to play a central role in the progressive neural morbidity that underlies neurodegenerative disorders such as Huntington’s Disease (HD), Alzheimer’s Disease (AD), and Parkinson’s Disease (PD). However, there is little current understanding of the link between in vivo neuroinflammation and in vivo brain atrophy in humans, particularly as it relates to how the disease spreads to regions beyond primary sites of pathology. In this study, we will use a novel multi-modal neuroimaging approach that combines positron emission tomography (PET), magnetic resonance spectroscopy (MRS), and magnetic resonance imaging (MRI) to investigate the contribution of neuroinflammation to brain atrophy in individuals with neurodegenerative disorders. This work has direct implications for (i) developing more complete models of the pathological processes underpinning disease expression, (ii) assessing the sensitivity of neuroinflammatory measures as disease biomarkers, and (iii) providing support for (or against) the value of pursing novel disease monitoring and intervention approaches that respectively involve measuring or mitigating chronic neuroinflammatory processes.

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