Alzheimer’s disease (AD) is the leading cause of dementia worldwide, yet its molecular mechanisms remain poorly understood. Numerous studies have shown that soluble oligomers of the amyloid-ß peptide (Aß1-42) are the earliest and most toxic forms in the amyloid cascade, responsible for initial neuronal damage prior to plaque formation. However, their intrinsic instability makes them difficult to study.
This project aims to design stable analogues of the Aß peptide capable of organizing into well-defined oligomeric forms, particularly tetramers and octamers. These species will be structurally and pharmacologically characterized to better understand their neurotoxic effects and interactions with neuronal membranes.
Fluorescent probes developed in the laboratory will enable the tracking of these species in cellular models and in vivo, through a collaboration with Dr. Nadja Van Camp (MIRCen).
The expected results will help identify the Aß forms truly responsible for neurodegeneration, pave the way for more selective therapeutic strategies, and support the development of innovative approaches for the early diagnosis of Alzheimer’s disease.