Lopez-Picon, F.R., Snellaman, A, Eskola, O, Helin, S, Trigg, W, Solin, O, Haaparanta-Solin, M and Rinne, J.O. (2017) Neuroinflammation appears early and then plateaus in a mouse model of Alzheimer´s disease shown by PET imaging. Journal of Nuclear Medicine (Oct 06). ISSN 0161-55052159-662X

Abstract

Rationale: Neuroinflammation has been associated with different neurological diseases including Alzheimer’s disease. In Alzheimer’s disease the translocator protein 18kDa (TSPO) is overexpressed in the activated microglia that surround the β-amyloid plaques. In the current study we aimed to study the association between β-amyloid deposition and neuroinflammation in a longitudinal study in a mouse model of 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 APP23 mouse model of Alzheimer’s disease. Immunohistochemistry was also used to study the β-amyloid and activated microglia in the mouse brain tissue. Results: The longitudinal study from 17 to 26 months of age showed robust increased binding of 11C-PIB with aging in the frontal cortex, parietotemporal cortex, hippocampus and thalamus of APP23 mice while the increase in 18F-GE-180 binding with the aging was minimal in the areas of early amyloidosis such as frontal cortex and hippocampus. A clear positive correlation between β-amyloid deposition and neuroinflammation as detected with 11C-PIB and 18F-GE-180 was obtained only in the parietotemporal cortex, and thalamus. Conclusion: 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 earlier stage of pathogenesis, while the amyloidosis continues to increase. We suggest that TSPO can be a good marker for early pathogenesis detection, but not for the long-term progression of the disease process.

Item Type:	Article
Date Deposited:	28 Oct 2017 00:45
Last Modified:	28 Oct 2017 00:45
URI:	https://oak.novartis.com/id/eprint/33488