title: Plaque-associated lipids in Alzheimer's diseased brain tissue visualized by nonlinear microscopy.
abstract: 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 β-amyloid (Aβ) plaques. Two lipid morphologies can be observed; lamellar structures and coalescing macro-aggregates of sub-micron sizes to ~25 μm. No significant lipid deposits were observed in non-fibrillar, diffuse plaques identified by Aβ 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 β-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 Aβ plaques, rendering them more dynamic compositions than previously believed and, hence, potential sources of toxic oligomers.
authors: Department of Biology and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
authors: Juris
authors: J
authors: Kiskis
authors: Department of Biology and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
authors: Helen
authors: H
authors: Fink
authors: Department of Biology and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
authors: Lena
authors: L
authors: Nyberg
authors: K-Analys, Salagatan 16 A, Uppsala, 753 30, Sweden.
authors: Jacob
authors: J
authors: Thyr
authors: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors: Jia-Yi
authors: JY
authors: Li
authors: Department of Biology and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
authors: Annika
authors: A
authors: Enejder
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D005453:Fluorescence; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008853:Microscopy / Q000379:methods*; D017711:Nonlinear Dynamics; D058225:Plaque, Amyloid / Q000473:pathology*; D013059:Spectrum Analysis, Raman
chemical_list: D008055:Lipids