Viscoelasticity of Amyloid Plaques in Transgenic Mouse Brain Studied by Brillouin Microspectroscopy and Correlative Raman Analysis
Journal of Innovative Optical Health Sciences
World Scientific Publishing
Amyloidopathy, one of the most prominent hallmarks of Alzheimer’s disease - the leading cause of dementia worldwide, is characterized by the accumulation of amyloid plaques in the brain parenchyma. The plaques consist of abnormal deposits mainly composed of an aggregation-prone protein fragment, -amyloid 1-40/1-42, into the extracellular matrix. Brillouin microspectroscopy is an all-optical contactless technique that, based on the interaction between visible light and longitudinal acoustic waves or phonons, gives access to the viscoelasticity of a sample on a subcellular scale. Here we describe the first application of micromechanical mapping based on Brillouin scattering spectroscopy to probe the stiffness of individual amyloid plaques in the hippocampal part of the brain of a -amyloid overexpressing transgenic mouse. Correlative analysis based on Brillouin and Raman microspectroscopy showed that amyloid plaques have a complex structure, with a rigid core of beta-pleated sheet conformation (-amyloid) protein surrounded by a softer ring-shaped region richer in lipids and other protein conformations. These preliminary results give a new insight into the plaque biophysics and biomechanics, and a valuable contrast mechanism for the study and diagnosis of amyloidopathy.
This work was generously supported by the Wellcome Trust Institutional Strategic Support Award (WT105618MA). This work was also supported by the Engineering and Physical Sciences Research Council (EP/M028739/1). The TASTPM mice were supplied by Eli Lilly Pharmaceuticals (UK) as part of the European Union’s Pharmacog initiative of which Prof Andrew D. Randall was member. His contribution to this work is acknowledged.
This is the author accepted manuscript. The final version is freely available from World Scientific Publishing via the DOI in this record.
Published: 21 April 2017