TSPO and amyloid deposits in sub-regions of the hippocampus in the 3xTgAD mouse model of Alzheimer's disease

Abstract

The involvement of the 18kDa translocator protein (TSPO), a marker of neuroinflammation, in Alzheimer's disease (AD) remains controversial. In the present report, we used [¹²⁵I]-CLINDE, a SPECT TSPO radiotracer never before used in AD, and we investigated the relationship between TSPO and amyloid plaque density (using [¹²⁵I]-DRM106) in a triple transgenic mouse model of AD (3xTgAD, APP_SWE, PS1_M146V and Tau_P301L). Our results show that TSPO increases appear before those of amyloid deposits. Moreover, the different parts of the hippocampus are differentially affected. Indeed, for both TSPO and amyloid, the subiculum is affected earlier and the ventral hippocampus later than the dorsal hippocampus. In the subiculum and the dorsal hippocampus of 3xTgAD mice, a positive correlation between TSPO and of amyloid deposit levels is observed. This data supports the hypothesis that TSPO could be used as a predictive marker of amyloid pathology. In addition, our immunohistochemical data shows a segregation of TSPO in the hippocampus and immunofluorescence imaging revealed a mainly microglial origin of the TSPO expression. Thus, imaging TSPO with CLINDE may be a good alternative to PET radiotracers.

Keywords: 3xTgAD; Alzheimer’s disease; CLINDE; DRM106; Neuroinflammation; TSPO.