Correlative cryo-soft X-ray tomography and cryo-structured illumination microscopy reveal changes to lysosomes in amyloid-β-treated neurons

DOI: 10.1016/j.str.2024.02.010

Authors: Karen E. Marshall (University of Sussex) , Kurtis Mengham (University of Sussex) , Matthew C. Spink (Diamond Light Source) , Lyra Vania (University of Sussex) , Hannah J. Pollard (University of Sussex) , Michele C. Darrow (Diamond Light Source) , Elizabeth Duke (Diamond Light Source) , Maria Harkiolaki (Diamond Light Source) , Louise C. Serpell (University of Sussex)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure , VOL 82

State: Published (Approved)
Published: March 2024
Diamond Proposal Number(s): 14508 , 20326 , 18833 , 18312

Abstract: Protein misfolding is common to neurodegenerative diseases (NDs) including Alzheimer’s disease (AD), which is partly characterized by the self-assembly and accumulation of amyloid-beta in the brain. Lysosomes are a critical component of the proteostasis network required to degrade and recycle material from outside and within the cell and impaired proteostatic mechanisms have been implicated in NDs. We have previously established that toxic amyloid-beta oligomers are endocytosed, accumulate in lysosomes, and disrupt the endo-lysosomal system in neurons. Here, we use pioneering correlative cryo-structured illumination microscopy and cryo-soft X-ray tomography imaging techniques to reconstruct 3D cellular architecture in the native state revealing reduced X-ray density in lysosomes and increased carbon dense vesicles in oligomer treated neurons compared with untreated cells. This work provides unprecedented visual information on the changes to neuronal lysosomes inflicted by amyloid beta oligomers using advanced methods in structural cell biology.

Subject Areas: Biology and Bio-materials


Instruments: B24-Cryo Soft X-ray Tomography

Added On: 13/03/2024 10:33

Documents:
1-s2.0-S0969212624000492-main.pdf

Discipline Tags:

Neurodegenerative Diseases Health & Wellbeing Neurology Structural biology Life Sciences & Biotech

Technical Tags:

Imaging Tomography Cryo-soft X-ray Tomography (Cryo-SXT)