A computational suite for the structural and functional characterization of amyloid aggregates
Open accessAbstract
We developed the aggregate characterization toolkit (ACT), a fully automated computational suite based on existing and widely used core algorithms to measure the number, size, and permeabilizing activity of recombinant and human-derived aggregates imaged with diffraction-limited and super-resolution microscopy methods at high throughput. We have validated ACT on simulated ground-truth images of aggregates mimicking those from diffraction-limited and super-resolution microscopies and showcased its use in characterizing protein aggregates from Alzheimer's disease. ACT is developed for high-throughput batch processing of images collected from multiple samples and is available as an open-source code. Given its accuracy, speed, and accessibility, ACT is expected to be a fundamental tool in studying human and non-human amyloid intermediates, developing early disease stage diagnostics, and screening for antibodies that bind toxic and heterogeneous human amyloid aggregates.
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The technique used to quantify soluble Aβ aggregates has previously been validated in multiple studies and specifically detects aggregates, not monomers.
“The technique used to quantify soluble aggregates has previously been validated in multiple studies and has been shown to specifically detect aggregates, and not monomers [29–31].”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [29]
The Introduction (page unavailable) describes SiMPull as an established assay for counting soluble aggregates, and the Results and discussion report validation of the ACT analysis toolkit using Aβ aggregates. Our copy does not establish that the assay detects aggregates but not monomers, or document validation of that specificity across multiple studies. (LLM, conf=0.82)
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BackgroundMethodInfluentialLecanemab preferentially binds to smaller aggregates present at early Alzheimer's disease
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Self-citationEarly synaptic pathology is associated with small tau aggregates in Alzheimer’s diseasePreprint
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- Authors
- Xia, Z., Wu, Y., Lam, J. Y. L., Zhang, Z., Burke, M., Fertan, E., Ranasinghe, R. T., Hidari, E., Danial, J. S. H., & Klenerman, D.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Danial, John S.H.
- Klenerman, David
- ORCID
- Venue
- Cell Reports Methods
- Publisher
- Elsevier BV
- Published
- 2023-06
- Volume
- 3
- Issue
- 6
- Pages
- 100499
- ISSN
- 2667-2375 (ISSN-L)
- PMC
- PMC10326375
- OpenAlex
- W4380370181
- Cited by
- 13
- References
- 30
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 2
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports Methods (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- King's College London
- Croucher Foundation
- Medical Research Council
- UK Dementia Research Institute
- Royal Society
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- amyloid aggregates, protein aggregation, super-resolution microscopy, Alzheimer's disease, high-throughput image analysis, automated image analysis, antibody screening
- MeSH terms
- Algorithms, Alzheimer Disease, Amyloid, Humans, Amyloidogenic Proteins, Protein Aggregates
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