Super‐Resolution Infrared Imaging of Polymorphic Amyloid Aggregates Directly in Neurons

Research output: Contribution to journalArticle

Abstract

Loss of memory during Alzheimer's disease (AD), a fatal neurodegenerative disorder, is associated with neuronal loss and the aggregation of amyloid proteins into neurotoxic β‐sheet enriched structures. However, the mechanism of amyloid protein aggregation is still not well understood due to many challenges when studying the endogenous amyloid structures in neurons or in brain tissue. Available methods either require chemical processing of the sample or may affect the amyloid protein structure itself. Therefore, new approaches, which allow studying molecular structures directly in neurons, are urgently needed. A novel approach is tested, based on label‐free optical photothermal infrared super‐resolution microspectroscopy, to study AD‐related amyloid protein aggregation directly in the neuron at sub‐micrometer resolution. Using this approach, amyloid protein aggregates are detected at the subcellular level, along the neurites and strikingly, in dendritic spines, which has not been possible until now. Here, a polymorphic nature of amyloid structures that exist in AD transgenic neurons is reported. Based on the findings of this work, it is suggested that structural polymorphism of amyloid proteins that occur already in neurons may trigger different mechanisms of AD progression.

Details

Authors
Organisations
External organisations
  • Synchrotron SOLEIL
  • Photothermal Spectroscopy Corporation
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • Optical photothermal infrared spectroscopyon, Alzheimer’s disease, protein aggregation, structure-function relation, disease mechanism, super-resolution, Alzheimer’s disease, aggregation, structure-function
Original languageEnglish
Article number1903004
Number of pages9
JournalAdvanced Science
Publication statusPublished - 2020 Feb 7
Publication categoryResearch
Peer-reviewedYes