Neuroinflammation Appears Early on PET Imaging and Then Plateaus in a Mouse Model of Alzheimer Disease

FR Lopez-Picon, A Snellman, O Eskola, S Helin, Olof Solin, M Haaparanta-Solin, JO Rinne

Research output: Contribution to journalArticleScientificpeer-review

21 Citations (Scopus)

Abstract

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.
Original languageUndefined/Unknown
Pages (from-to)509–515
Number of pages7
JournalJournal of Nuclear Medicine
Volume59
Issue number3
DOIs
Publication statusPublished - 2018
MoE publication typeA1 Journal article-refereed

Keywords

  • GE-180
  • PIB
  • Alzheimer disease
  • beta-amyloid
  • Neuroinflammation

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