CARS & Raman micro- and nanoscopy of the molecular mechanisms behind Alzheimer´s disease

Research Project, 2011 – 2015

We propose to develop an innovative microscopy technique to monitor the intriguing molecular processes behind Alzheimer´s disease (AD), combining 1. imaging of the 3D distribution of proteins and lipids in and around AD plaques utilizing the Coherent Anti-Stokes Raman (CARS) process and point-wise Raman spectroscopy of their full chemical and physical properties (alfa-helix/beta-sheet, degree of oxidation/stress damage). 2. far-field CARS/Raman microscopy of the molecular composition of AD plaques and neurons at ~400 nm resolution and near-field CARS/Raman imaging of the detailed macromolecular architecture at ~80 nm resolution by means of a 50 nm-sized NSOM fiber probe. Plaque formation will be studied (i) in a model system consisting of â-amyloid monomers, oligomers, fibrils and relevant membrane lipids (ii) in real-time in cultured AD neurons, (iii) in transgenic mouse models of AD, and (iv) in AD samples from human brain banks. Unique visual information is expected: the full kinetics of the protein misfolding mechanisms from early to advanced stages, the role of membrane lipids in this process, and the influence of the local chemical and biological environment in general.