TY - JOUR
T1 - Label-free Raman and fluorescence imaging of amyloid plaques in human Alzheimer's disease brain tissue reveal carotenoid accumulations
AU - Ettema, Loes
AU - Lochocki, Benjamin
AU - Hoozemans, Jeroen J. M.
AU - de Boer, Johannes F.
AU - Ariese, Freek
N1 - Funding Information: This research is supported by the Dutch Technology Foundation STW (Grant Number 13935, I-READ), which is part of the Netherlands Organization of Scientific Research (NWO), and which is partly funded by the Ministry of Economic Affairs. Publisher Copyright: © 2022 The Author(s). Published by IOP Publishing Ltd.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Alzheimer's disease (AD) is a neurodegenerative disease, characterized by the presence of extracellular deposits (plaques) of amyloid-beta peptide and intracellular aggregates of phosphorylated tau. In general, these hallmarks are studied by techniques requiring chemical pre-treatment and indirect labeling. Imaging techniques that require no labeling and could be performed on tissue in its native form could contribute to a better understanding of the disease. In this article a combination of label-free and non-invasive techniques is presented to study the biomolecular composition of AD human brain tissue. We build on previous research that already revealed the autofluorescence property of plaque, and the presence of carotenoids in cored plaques. Here, we present further results on cored plaques: showing blue and green autofluorescence emission coming from the same plaque location. Raman microscopy was used to confirm the presence of carotenoids in the plaque areas, with clear peaks around 1150 and 1514 cm-1. Carotenoid reference spectra were recorded in hexane solution, but also adsorbed on aggregated Aβ42 peptides; the latter agreed better with the Raman spectra observed in plaques. From the six single carotenoids measured, lycopene matched closest with the peak positions observed in the cored plaques. Lastly, stimulated Raman scattering (SRS) microscopy measurements were performed, targeting the shift of the beta-sheet Amide I peak observed in plaques. Employing SRS in the C-H stretch region we also looked for the presence of a lipid halo around plaque, as reported in the literature for transgenic AD mice, but such a halo was not observed in these human AD brain samples.
AB - Alzheimer's disease (AD) is a neurodegenerative disease, characterized by the presence of extracellular deposits (plaques) of amyloid-beta peptide and intracellular aggregates of phosphorylated tau. In general, these hallmarks are studied by techniques requiring chemical pre-treatment and indirect labeling. Imaging techniques that require no labeling and could be performed on tissue in its native form could contribute to a better understanding of the disease. In this article a combination of label-free and non-invasive techniques is presented to study the biomolecular composition of AD human brain tissue. We build on previous research that already revealed the autofluorescence property of plaque, and the presence of carotenoids in cored plaques. Here, we present further results on cored plaques: showing blue and green autofluorescence emission coming from the same plaque location. Raman microscopy was used to confirm the presence of carotenoids in the plaque areas, with clear peaks around 1150 and 1514 cm-1. Carotenoid reference spectra were recorded in hexane solution, but also adsorbed on aggregated Aβ42 peptides; the latter agreed better with the Raman spectra observed in plaques. From the six single carotenoids measured, lycopene matched closest with the peak positions observed in the cored plaques. Lastly, stimulated Raman scattering (SRS) microscopy measurements were performed, targeting the shift of the beta-sheet Amide I peak observed in plaques. Employing SRS in the C-H stretch region we also looked for the presence of a lipid halo around plaque, as reported in the literature for transgenic AD mice, but such a halo was not observed in these human AD brain samples.
KW - A beta
KW - A β
KW - Alzheimer's disease
KW - Raman spectroscopy
KW - amyloid
KW - lipid
KW - plaques
KW - protein
UR - http://www.scopus.com/inward/record.url?scp=85128666205&partnerID=8YFLogxK
U2 - https://doi.org/10.1088/2040-8986/ac5b51
DO - https://doi.org/10.1088/2040-8986/ac5b51
M3 - Article
SN - 2040-8978
VL - 24
SP - 1
EP - 12
JO - Journal of Optics (United Kingdom)
JF - Journal of Optics (United Kingdom)
IS - 5
M1 - 054005
ER -