Neuroinflammation has been associated with various neurologic diseases, including Alzheimer disease (AD). In AD, the translocator protein 18 kDa (TSPO) is overexpressed in the activated microglia that surround the beta-amyloid plaques. In the current longitudinal study using a mouse model of AD, we evaluated the association between beta-amyloid deposition and neuroinflammation in AD. Methods: To monitor the longitudinal changes in b-amyloid deposition and neuroinflammation, we used in vivo PET imaging and ex vivo autoradiography with Pittsburgh compound B (C-11-PIB) and a TSPO tracer, flutriciclamide (F-18-GE-180), in the APP23 mouse model of AD. We also applied immunohistochemistry to study beta-amyloid and activated microglia in the mouse brain tissue. Results: From 17 to 26 mo of age, the mice showed robust increased binding of C-11-PIB with aging in the frontal cortex, parietotemporal cortex, hippocampus, and thalamus whereas the increase in F-18-GE-180 binding with aging was minimal in areas of early amyloidosis such as the frontal cortex and hippocampus. A clear positive correlation between beta-amyloid deposition and neuroinflammation was detected with C-11-PIB and F-18-GE-180 only in the parietotemporal cortex and thalamus. Conclusion: The neuroinflammation increase detected with F-18-GE-180 is less than the increase in amyloidosis detected with C-11-PIB. Furthermore, binding of F-18-GE-180 plateaus at an earlier stage of pathogenesis whereas amyloidosis continues to increase. We suggest that TSPO can be a good marker for early pathogenesis detection but not for tracking long-term disease progression.
|Number of pages||7|
|Journal||Journal of Nuclear Medicine|
|Publication status||Published - 2018|
|MoE publication type||A1 Journal article-refereed|
- Alzheimer disease