Alzheimer's disease(AD)is the most common cause of dementia,costing about 1%of the global economy.Failures of clinical trials targeting amyloid-βprotein(Aβ),a key trigger of AD,have been explained by drug ineffi...Alzheimer's disease(AD)is the most common cause of dementia,costing about 1%of the global economy.Failures of clinical trials targeting amyloid-βprotein(Aβ),a key trigger of AD,have been explained by drug inefficiency regardless of the mechanisms of amyloid neurotoxicity,which are very difficult to address by available technologies.Here,we combine two imaging modalities that stand at opposite ends of the electromagnetic spectrum,and therefore,can be used as complementary tools to assess structural and chemical information directly in a single neuron.Combining label-free super-resolution microspectroscopy for sub-cellular imaging based on novel optical photothermal infrared(O-PTIR)and synchrotron-based X-ray fluorescence(S-XRF)nano-imaging techniques,we capture elemental distribution and fibrillary forms of amyloid-βproteins in the same neurons at an unprecedented resolution.Our results reveal that in primary AD-like neurons,iron clusters co-localize with elevated amyloidβ-sheet structures and oxidized lipids.Overall,our O-PTIR/S-XRF results motivate using high-resolution multimodal microspectroscopic approaches to understand the role of molecular structures and trace elements within a single neuronal cell.展开更多
基金O.K.:Swedish Research Council Starting Grant 2017-01539,Vinnova 2019-02554,Grafoord 20190755,Swedish Brain Foundation F02020-0315,Royal Physiographic Society of LundAke Wiberg Stiftelse 203057,and Swedish Research Council grant 2015-02656 of G.K.G.
文摘Alzheimer's disease(AD)is the most common cause of dementia,costing about 1%of the global economy.Failures of clinical trials targeting amyloid-βprotein(Aβ),a key trigger of AD,have been explained by drug inefficiency regardless of the mechanisms of amyloid neurotoxicity,which are very difficult to address by available technologies.Here,we combine two imaging modalities that stand at opposite ends of the electromagnetic spectrum,and therefore,can be used as complementary tools to assess structural and chemical information directly in a single neuron.Combining label-free super-resolution microspectroscopy for sub-cellular imaging based on novel optical photothermal infrared(O-PTIR)and synchrotron-based X-ray fluorescence(S-XRF)nano-imaging techniques,we capture elemental distribution and fibrillary forms of amyloid-βproteins in the same neurons at an unprecedented resolution.Our results reveal that in primary AD-like neurons,iron clusters co-localize with elevated amyloidβ-sheet structures and oxidized lipids.Overall,our O-PTIR/S-XRF results motivate using high-resolution multimodal microspectroscopic approaches to understand the role of molecular structures and trace elements within a single neuronal cell.
