Investigating Aβ plaque development using FTIR micro‐spectroscopy on native postmortem human brain tissue

Abstract

AbstractBackgroundFourier‐transform infrared microspectroscopy (FTIR) enables the resolution of various chemical compounds and the secondary structure of proteins in tissue sections1. We used FTIR to investigate Aβ plaques with regard to their supposed development process from diffuse to cored plaques. A central process in plaque formation is the misfolding of Aβ and its subsequent assembly into β‐pleated fibrils, which accumulate in amyloid deposits. Misfolded Aβ is believed be neurotoxic and to exhibit oxidative properties2. We aim to contribute to the understanding of mechanisms that lead to the emergence of Aβ plaques and processes that are associated with the characteristic plaque morphologies.MethodFTIR was performed on native human brain sections from AD cases (n = 7, plus 3 control cases). Subsequent immunohistochemical staining against Aβ was performed on the same tissue section. In cooperation with neuropathology experts we conducted a spectral analysis of specific plaque types (N = 167 plaques total), with annotations based on well‐described morphologies (diffuse, compact, classic cored).ResultWe observed increased contents of β‐sheet protein in different plaque types and interpret these findings with regards to proposed maturation sequences3. A red‐shift of the Amid 1 absorbance band suggests the formation of fibrils in plaques. Additionally, we investigated the lipid composition in different plaque types and compared these findings to previously described lipid alterations in AD brain4.ConclusionBy clarifying the relationship between Aβ fibrillation and different plaque types, we give evidence to hypotheses regarding plaque maturation. Our investigation of lipid alterations in plaques illuminate the neurotoxicity of Aβ and its relevance in AD pathology from a different angle. The capability to examine proteins and lipids simultaneously, marker‐free and under native conditions emphasize the research potential of vibrational spectroscopy in neurodegeneration5.