TSPO-PET for the Prediction and Monitoring of Immunomodulatory Effects in Alzheimer's Disease Mouse Models in Conjunction with Amyloid- and Tau-Imaging

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Molecular imaging with positron emission tomography (PET) facilitates the investigation of neuropathological hallmarks of Alzheimers disease (AD) in vivo. In addition to the well-known protein depositions, i.e. beta-amyloid plaques and hyperphosphorylated tau-fibrils, the activation of microglia represents an inflammatory component of AD pathophysiology. Our group has contributed importantly in a worldwide effort towards developing novel PET tracers for visualizing neuropathological markers in transgenic AD mouse models. The major aims of the current research project follow in a sequence. First, we shall investigate microglial activation in relation with abnormal protein deposition in different transgenic beta-amyloid and tau mouse models, along with complementary behavioral/cognitive assessment using the Morris-Water- and Y-Mazes. After completion of the longitudinal PET/behavioral study, we shall confirm pathology by histopathological and biochemical assessments. In the second stage of this project, we shall test the efficacy of acute and chronic immunomodulatory therapeutics on the progression of beta-amyloid- and tau-load in the AD mice, emphasizing the predictive value of the neuroinflammation-PET on the effects of immunomodulation on the cognitive testing and in vitro histopathological outcomes. In the final stage, we shall test the effect of an anti-beta-amyloid vaccination on the neuroinflammatory response, and on the progression of amyloidopathy and impaired cognitive performance in AD mice. Given that anti-beta-amyloid vaccines have already entered human trials, we are convinced of the translation relevance of the current project.