Open AccessSuper‐Resolution Infrared Imaging of Polymorphic Amyloid Aggregates Directly in Neurons
Author(s) -
Klementieva Oxana,
Sandt Christophe,
Martinsson Isak,
Kansiz Mustafa,
Gouras Gunnar K.,
Borondics Ferenc
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201903004
Subject(s) - amyloid (mycology) , neurite , protein aggregation , protein folding , biophysics , dendritic spine , neuroscience , amyloidosis , chemistry , neurodegeneration , biology , biochemistry , pathology , medicine , in vitro , disease , inorganic chemistry , hippocampal formation
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.