Plaque-associated lipids in Alzheimer's diseased brain tissue visualized by nonlinear microscopy

By simultaneous coherent anti-Stokes Raman scattering (CARS) and 2-photon fluorescence microscopy of Thioflavin-S stained Alzheimer's diseased human brain tissues, we show evidence of lipid deposits co-localizing with fibrillar beta-amyloid (A beta) plaques. Two lipid morphologies can be observed; lamellar structures and coalescing macro-aggregates of sub-micron sizes to similar to 25 mu m. No significant lipid deposits were observed in non-fibrillar, diffuse plaques identified by A beta immuno-staining. CARS microscopy of unlabeled samples confirms the lamellar and macro-aggregate lipid morphologies. The composition of the plaques was analyzed by CARS microspectroscopy and Raman microscopy; vibrational signatures of lipids with long acyl chains co-localize with the beta-sheet vibrations. The lipid fluidity was evaluated from the CARS spectra, illustrating that the lipid composition/organization varies throughout the plaques. Altogether this indicates close amyloid-lipid interplay in fibrillar A beta plaques, rendering them more dynamic compositions than previously believed and, hence, potential sources of toxic oligomers.