Earlier this year, a study proposed by Dr. Todd Cohen (PI) and Dr. Rick Meeker (Co-PI) was selected by the SOM for funding as ECBR grant award. The study is titled “Inflammation, Aging and Alzheimer Disease Vulnerability”. (Click Title to read more)
The Cohen and Meeker group identified a unique and previously unrecognized form of Tau recognized by the Tau1 antibody but not other antibodies used to detect Alzheimer pathology. This form of Tau not only appears during the earliest stages of inflammation-associated neuronal pathology but also develops naturally in aging mice. The age- and inflammation-dependent accumulation of this form of Tau suggest that it may be an important link between these risk factors and AD pathogenesis. The study aims to characterize the development of pathological effects of Tau overexpression in both normal aged and Alzheimer mouse model.
In this study, non-invasive MRI and PET imaging will be used to delineate changes on structure, molecular and functional activity in these animal models. Specifically, neural inflammation level will be measured by PET imaging with PBR-111 probe. Level of synaptic vesicle glycoprotein 2A will be measured as an indicator of synaptic density by PET imaging with 11C-UCB-J probe. MRI scan will be also performed on the same animal to provide anatomical references and any structure changes within brain. Imaging results will be validated by immunostaining with Iba-1 and synaptophysin, and will be further used to correlate electrophysiology, cognitive function, and the expression level of Tau1 in these animal models.
The study is a broad collaboration among experts on Tau pathology, neuroinflammation, electrophysiology, behavior science, and imaging science. It will provide synergistic information on the relationship between early Tau modifications and the development of neural dysfunction.