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Single-molecule detection methods to study alpha-synuclein aggregation in postmortem Parkinson's disease brains.

Overview

Authors: Emre Fertan1,2, John S.H. Danial1,2, Stephen Neame3, Jeff Y.L. Lam1,2, Matthew W. Cotton1,2, Melanie Burke1,2, Zengjie Xia1,2, Yunzhao Wu1,2, Ben Powney3, Yoichi Imaizumi3, Annelies Quaegebeur4, Georg Meisl1,2, James Staddon3, David Klenerman1,2
ORCID iDs: John S.H. Danial, David Klenerman
  1. Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
  2. UK Dementia Research Institute at University of Cambridge, Cambridge CB2 0XY, UK
  3. Eisai Ltd., EMEA Knowledge Centre, Mosquito Way, Hatfield AL10 9SN, UK
  4. Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK
Institutions: University of Cambridge (United Kingdom); UK Dementia Research Institute (United Kingdom); Eisai (United Kingdom) (United Kingdom)
Journal: Cell reports methods, volume 6, issue 6, article 101418
Dates: received 7 July 2025; accepted 26 March 2026; published online 23 April 2026; in print June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.crmeth.2026.101418 · PMID 42030949 · PMCID PMC13282648 · OpenAlex W7155389954
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: other (modality), histology / microscopy (modality), human (organism), mouse (organism), Parkinson's (population), pain (population), cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics
Keywords: single-molecule detection, DNA-PAINT, SIMOA, soluble aggregate, diffusible aggregate, mouse model, Triton X-100, sarkosyl, extraction, data modeling
MeSH: alpha-Synuclein*, Brain*, Parkinson Disease*, Protein Aggregates*, Protein Aggregation, Pathological*, Single Molecule Imaging*, Animals, Disease Models, Animal, Female, Humans, Male, Mice (* major topic)
Topic: Parkinson's Disease Mechanisms and Treatments (Neurology, Medicine), according to OpenAlex
Funding: The Royal Society; UK Dementia Research Institute; Alzheimer’s Research UK (ARUK-PG2020A-009); Alzheimer's Society; UK Research and Innovation Medical Research Council; Eisai
Citations: cited by 1 paper (Europe PMC); 50 references in the paper
Research resources: Mouse Monoclonal anti-alpha Synuclein RRID:AB_1954821, Mouse: Line 61 RRID:IMSR_JAX:038796

Abstract

Nanoscopic aggregates of alpha-synuclein (ɑSyn) have been observed in Parkinson’s 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 single molecule array (SIMOA), and super-resolution microscopy to quantify and characterize ɑSyn aggregates harvested from human brain samples, alongside a mouse model of synucleinopathy, 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 suggest that ɑSyn aggregates slowly in the brain, leading to formation of larger aggregates in a sub-set of cells.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

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Data

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Data and code availability

• Data reported in this paper will be shared by the lead contact upon request. • This paper does not report original code. • Any additional information required to analyze the data reported in this paper is available from the lead contact upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 10 keywords, 12 MeSH terms, 6 funders, 50 references, 2 RRIDs.

Cite

This paper

Fertan, E., Danial, J. S., Neame, S., Lam, J. Y., Cotton, M. W., Burke, M., Xia, Z., Wu, Y., Powney, B., Imaizumi, Y., Quaegebeur, A., Meisl, G., Staddon, J., & Klenerman, D. (2026). Single-molecule detection methods to study alpha-synuclein aggregation in postmortem Parkinson's disease brains. Cell reports methods, 6(6), 101418. https://doi.org/10.1016/j.crmeth.2026.101418

BibTeX

@article{fertan2026single,
author = {Fertan, Emre and Danial, John S.H. and Neame, Stephen and Lam, Jeff Y.L. and Cotton, Matthew W. and Burke, Melanie and Xia, Zengjie and Wu, Yunzhao and Powney, Ben and Imaizumi, Yoichi and Quaegebeur, Annelies and Meisl, Georg and Staddon, James and Klenerman, David},
title = {{Single-molecule detection methods to study alpha-synuclein aggregation in postmortem Parkinson's disease brains}},
journal = {Cell reports methods},
year = {2026},
month = apr,
volume = {6},
number = {6},
pages = {101418},
publisher = {Elsevier},
issn = {2667-2375},
doi = {10.1016/j.crmeth.2026.101418},
url = {https://doi.org/10.1016/j.crmeth.2026.101418},
pmid = {42030949},
pmcid = {PMC13282648}
}

RIS

TY - JOUR
AU - Fertan, Emre
AU - Danial, John S.H.
AU - Neame, Stephen
AU - Lam, Jeff Y.L.
AU - Cotton, Matthew W.
AU - Burke, Melanie
AU - Xia, Zengjie
AU - Wu, Yunzhao
AU - Powney, Ben
AU - Imaizumi, Yoichi
AU - Quaegebeur, Annelies
AU - Meisl, Georg
AU - Staddon, James
AU - Klenerman, David
TI - Single-molecule detection methods to study alpha-synuclein aggregation in postmortem Parkinson's disease brains
T2 - Cell reports methods
J2 - Cell Rep Methods
PY - 2026
DA - 2026/04/23
VL - 6
IS - 6
SP - 101418
SN - 2667-2375
PB - Elsevier
DO - 10.1016/j.crmeth.2026.101418
UR - https://doi.org/10.1016/j.crmeth.2026.101418
LA - en
ER -

CSL-JSON

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