Imaging disease associated astrogliosis by Positron Emission Tomography in Alzheimer’s disease

This PhD fellowship focuses on the assessment of astrocytic reactivity induced by tauopathy, associated with Alzheimer's disease, using PET imaging or 3D-autoradiography using the radioligand [11C]BU99008 or [3H]BU99008 specific for I2-BS receptors, target of astrocytic reactivity. The main objectives of this research project are: 1- to validate the specificity of the [11C]/[3H]BU99008 ligand binding in different models of tauopathy; 2- to characterise the signature of reactive astrocytes detected by BU99008; and 3- to assess the specific binding of [11C]/[3H]BU99008 as well as gene expression following a therapeutic strategy targeting I2-BS receptors in one of the tauopathy models. Our methodological approach adopts a multiscale perspective, combining PET imaging with microscopic and transcriptomic analyses, thus enabling a multiscale analysis ranging from macro (in vivo) to micro (in vitro). These studies not only provide a fundamental understanding of astrocytic reactivity, but also open important perspectives for the development of therapeutic strategies targeting astrocytic reactivity in the context of neurodegenerative diseases.