Overview
Neurodegeneration is the progressive dysfunction and loss of neurons, and is the hallmark feature of common dementing diseases such as Alzheimer’s, Parkinson’s, and dementia with Lewy bodies. Increasing evidence suggests that chronic immune activation of microglial cells plays a key role in the pathogenesis of neurodegeneration. PET ligands that label protein markers of microglial activation have been developed and found to be deposited in brain structures that are typically associated with the highest density of amyloid. This is consistent with human histopathological research suggesting that microglia accumulate around amyloid plaques. Microglia are involved in neurodegeneration in complex ways. They appear to have positive functions in some processes such as phagocytosis of and removal of amyloid from the brain and negative effects in other situations where they generate toxic inflammatory effects and cause or promote cell death. Understanding the complex relationship between microglial activation and cognitive dysfunction is crucial for the development of new therapeutic agents.
Projects related to neuroinflammation are conducted by the Center for Neurodegeneration and Translational Neuroscience. The CNTN was established in 2015 through a NIGMS-funded Center of Biomedical Research Excellence Grant (COBRE). The CNTN collects longitudinal data on a cohort of participants with AD, MCI, PD, and cognitively normal individuals. In addition to annual structural and functional MRI, a neuropsychological test battery, blood-based inflammatory markers, and amyloid PET scan, a subset of 70 participants undergo PET imaging with the GE-180 ligand. GE-180 is a newly developed radiotracer that binds to translocator protein (TSPO) in activated microglial cells. Increased TSPO binding indicates the transition of microglial from resting state to an active state and serves as an in vivo assessment of progression and severity of neuroinflammation.
Contact Information
Aaron Ritter, MD
rittera@ccf.org
Jessica Caldwell, PhD
caldwej5@ccf.org
Members & Collaborations
Cleveland Clinic Affiliations
- Virendra Mishra PhD
- Karthik Sreenivasan, MS
- Dietmar Cordes, PhD
External Relationships and Collaborations
- Sarah Banks, UCSD
- Jefferson Kinney, UNLV
