Alzheimer disease (AD) is characterized by the presence of two types characteristic lesions in the brain. Intraneuronal neurofibrillary tangles are formed by hyperphosphorylated microtubule-associated Tau protein. Extracellular senile plaques result from the deposition of β-amyloïd (Aβ) peptide, which is released from the amyloid precursor protein (APP). The progressive formation of the two lesions, along with the alteration of APP and Tau functions are core events in AD pathology.
Our group investigates how molecular interactions can affect APP processing/function and NFT formation. The exact function of APP in neurons remain poorly known. APP resembles a membrane receptor with its juxta-/transmembrane driving homo- and hetero-interactions. By over-expression of various APP isoforms and APP mutants, combined with down regulation approaches, we investigate the neuronal function of the protein both in vitro and in vivo. Our group also developed various mice model to address the pathophysiological role of Tau and to identify Tau-directed therapeutic targets.