RT Journal Article
T1 Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer's Disease.
A1 Paulus, Agnes
A1 Engdahl, Anders
A1 Yang, Yiyi
A1 Boza-Serrano, Antonio
A1 Bachiller, Sara
A1 Torres-Garcia, Laura
A1 Svanbergsson, Alexander
A1 Garcia, Megg G
A1 Gouras, Gunnar K
A1 Li, Jia-Yi
A1 Deierborg, Tomas
A1 Klementieva, Oxana
K1 Alzheimer’s disease
K1 FTIR
K1 Tau
K1 amyloid-β
K1 cellular environment
K1 α-synuclein β-sheet
AB Alzheimer's disease affects millions of lives worldwide. This terminal disease is characterized by the formation of amyloid aggregates, so-called amyloid oligomers. These oligomers are composed of β-sheet structures, which are believed to be neurotoxic. However, the actual secondary structure that contributes most to neurotoxicity remains unknown. This lack of knowledge is due to the challenging nature of characterizing the secondary structure of amyloids in cells. To overcome this and investigate the molecular changes in proteins directly in cells, we used synchrotron-based infrared microspectroscopy, a label-free and non-destructive technique available for in situ molecular imaging, to detect structural changes in proteins and lipids. Specifically, we evaluated the formation of β-sheet structures in different monogenic and bigenic cellular models of Alzheimer's disease that we generated for this study. We report on the possibility to discern different amyloid signatures directly in cells using infrared microspectroscopy and demonstrate that bigenic (amyloid-β, α-synuclein) and (amyloid-β, Tau) neuron-like cells display changes in β-sheet load. Altogether, our findings support the notion that different molecular mechanisms of amyloid aggregation, as opposed to a common mechanism, are triggered by the specific cellular environment and, therefore, that various mechanisms lead to the development of Alzheimer's disease.
YR 2021
FD 2021-03-26
LK https://hdl.handle.net/10668/25471
UL https://hdl.handle.net/10668/25471
LA en
DS RISalud
RD Apr 8, 2025