Neuroinflammation appears early and then plateaus in a mouse model of Alzheimer's disease shown by PET imaging

: Francisco R. López-Picón, Anniina Snellman, Olli Eskola, Semi Helin, Olof Solin, Merja Haaparanta-Solin, Juha O. Rinne

Publisher: SOC NUCLEAR MEDICINE INC

: 2018

: Journal of Nuclear Medicine

: Journal of nuclear medicine : official publication, Society of Nuclear Medicine

: J Nucl Med

: 59

: 3

: 509

: 515

: 7

: 1535-5667

DOI: https://doi.org/10.2967/jnumed.117.197608

Rationale: Neuroinflammation has been associated with different neurological diseases including Alzheimer's disease (AD). In AD, the translocator protein 18kDa (TSPO) is overexpressed in the activated microglia that surround the β-amyloid plaques. In the current longitudinal study, using a mouse model of AD, we evaluated the association between β-amyloid deposition and neuroinflammation in AD. Methods: To monitor the longitudinal changes in β-amyloid deposition and neuroinflammation, we used in vivo PET imaging and ex vivo autoradiography with 11C-PIB and a TSPO tracer, 18F-GE-180, in the APP23 mouse model of AD. We also applied immunohistochemistry to study β-amyloid and activated microglia in the mouse brain tissue. Results: From 17 to 26 months of age, the mice showed robust increased binding of 11C-PIB with aging in the frontal cortex, parietotemporal cortex, hippocampus, and thalamus while the increase in 18F-GE-180 binding with aging was minimal in areas of early amyloidosis such as frontal cortex and hippocampus. A clear positive correlation between β-amyloid deposition and neuroinflammation was detected with 11C-PIB, and 18F-GE-180 was obtained only in the parietotemporal cortex and thalamus. Conclusion: The neuroinflammation increase detected with 18F-GE-180 is less than the increase in amyloidosis detected with 11C-PIB. Furthermore, the binding of 18F-GE-180 plateaus at an earlier stage of pathogenesis whereas the 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.