Super-resolution microscopy of alpha-synuclein aggregates in brain samples indicates a subset of cells have disrupted protein homeostasis
Fertan, E.; Danial, J.; Neame, S.; Meisl, G.; Lam, J. Y. L.; Burke, M.; Xia, Z.; Wu, Y.; Powney, B.; Imaizumi, Y.; Quaegebeur, A.; Staddon, J.; Klenerman, D.
Show abstract
Nanoscopic aggregates of alpha-synuclein have been observed in Parkinsons disease (PD). However, the processes that occur in-vivo leading to the formation of these small aggregates are not well understood. We used ultra-sensitive single-molecule methods including SIMOA and super-resolution microscopy to quantify and characterise alpha-synuclein aggregates harvested from human brain samples alongside the Line 61 mouse model using different tissue processing methods. While aggregate numbers did not differ between PD and control samples, larger aggregates were detected in PD brain samples. Moreover, different sub-populations of aggregates were obtained by different extraction methods, with diffusible and membrane-bound aggregates producing a more pronounced difference between disease and control samples. Our data suggests that alpha-synuclein aggregates slowly in the brain, leading to formation of larger aggregates in a sub-set of cells.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity 96%
- Neuroprotection of low dose carbon monoxide in Parkinson's disease models commensurate with the reduced risk of Parkinson's among smokers 95%
- Novel tools to quantify total, phospho-Ser129 and aggregated alpha-synuclein in the mouse brain 95%
Similar papers in this journal
- Probe-dependent Proximity Profiling (ProPPr) Uncovers Similarities and Differences in Phospho-Tau-Associated Proteomes Between Tauopathies 94%
- Single molecule array measures of LRRK2 kinase activity in serum link Parkinson's disease severity to peripheral inflammation 94%
- Transcriptome deregulation of peripheral monocytes in GBA -related Parkinson’s disease 94%
Similar papers in this journal
Similar papers in this journal
- Glycated alpha-synuclein assemblies cause distinct Parkinsons disease pathogenesis in mice 95%
- Divergent age-dependent conformational rearrangement within Aβ-amyloid deposits in APP23, APPPS1, and AppNL-F mice 95%
- SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF Resulting in Drastic Soluble Protein Depletion 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.