Evidence map›Paper›PMID 39718440›Full record

ArticleAnalytical chemistry2025

Ultrasensitive Protein Aggregate Quantification Assays for Neurodegenerative Diseases on the Simoa Platform.

Dorothea Böken, Zengjie Xia, Jeff Y L Lam, Emre Fertan, Yunzhao Wu, Elizabeth A English, Juraj Konc, Florence Layburn, Gonçalo J L Bernardes, Henrik Zetterberg and 2 more

Erratum issuedAbstract read
In one paragraph

Article in Analytical chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
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  5. Article
  6. Article
  7. Article
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  9. Article
  10. Small-diffusible aggregates, plaques, tangles, and dynamic equilibria: Untangling Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  11. Lecanemab preferentially binds to smaller aggregates present at early Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  12. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Dorothea BökenYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.ORCID 0009-0008-8443-4469
Zengjie XiaYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.
Jeff Y L LamYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.
Emre FertanYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.
Yunzhao WuYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.
Elizabeth A EnglishYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.
Juraj KoncYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.
Florence LayburnYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.
Gonçalo J L BernardesYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.ORCID 0000-0001-6594-8917
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal 43139, Sweden.
Matthew R CheethamYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.
David KlenermanYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.

Funding

Medical Research Council MR/X021874/1
6 · The paper itself

Abstract

Nanoscale aggregates play a key role in the pathogenesis of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. However, quantifying these aggregates in complex biological samples, such as biofluids and postmortem brain tissue, has been challenging due to their low concentration and small size, necessitating the development of methods with high sensitivity and specificity. Here, we have developed ultrasensitive assays utilizing the Quanterix Simoa platform to detect α-synuclein, β-amyloid and tau aggregates, including those with common posttranslational modifications such as truncation of α-synuclein and AT8 phosphorylation of tau aggregates. All assays had a detection limit in the low pM range. As a part of this work, we developed silica-nanoparticle calibrators, allowing for the quantification of all aggregates. These assays were validated for aggregate and target specificity through denaturation and cross-reactivity experiments. We then applied these assays to brain homogenate samples from Alzheimer's disease and control samples, demonstrating their applicability to postmortem tissue. Lastly, we explored the potential of these assays for blood-based diagnostics by detecting aggregates in serum samples from early Alzheimer's disease patients.

Indexed as

alpha-SynucleinAlzheimer DiseaseAmyloid beta-PeptidesNeurodegenerative DiseasesProtein Aggregatestau ProteinsHumansLimit of DetectionSilicon Dioxidealpha-SynucleinAmyloid beta-PeptidesProtein AggregatesSilicon Dioxidetau Proteins

Identifiers

PMID39718440
PMCPMC11740166

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.