CARS and Raman microscopy of Alzheimer’s Brain Tissue

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder without cure, characterized by the presence of extracellular plaques surrounded by dystrophic neuritis . Fundamental understanding of the molecular processes involved is urgently needed in order to develop strategies to inhibit steps in the AD pathogenesis. Current understanding is that the senile plaques are composed of peptide fragments (Amyloid- β peptides) formed after the cleavage of the transmembrane protein amyloid protein precursor (APP) . This knowledge relies primarily on biochemical analysis of the plaques in cell extracts together with fluorescence microscopy of tissue samples exposed to harsh preparation procedures and labeling. Thus, it is disputed to which extent the observations reported reflect the true biochemistry and morphology of AD brain tissue. By the powerful combination of Raman microspectroscopy, Coherent Anti-Stokes Raman Scattering (CARS) and 2-photon fluorescence microscopy, we show that the molecular composition of AD plaques is more complex and consequently the mechanisms behind their formation.