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Quantitative detection of α-Synuclein and Tau oligomers and other aggregates by digital single particle counting
Blömeke L, Pils M, Kraemer-Schulien V, Dybala A, Schaffrath A, Kulawik A, Rehn F, Cousin A et al.. NPJ Parkinson's disease, 2022-06-02
Topic: Brain proteins, microglia and lab models
The pathological hallmark of neurodegenerative diseases is the formation of toxic oligomers by proteins such as alpha-synuclein (aSyn) or microtubule-associated protein tau (Tau). Consequently, such oligomers are promising biomarker candidates for diagnostics as well as drug development. However, measuring oligomers and other aggregates in human biofluids is still challenging as extreme sensitivity and specificity are required. We previously developed surface-based fluorescence intensity distribution analysis (sFIDA) featuring single-particle sensitivity and absolute specificity for aggregates. In this work, we measured aSyn and Tau aggregate concentrations of 237 cerebrospinal fluid (CSF) samples from five cohorts: Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and a neurologically-normal control group. aSyn aggregate concentration discriminates PD and DLB patients from normal controls (sensitivity 73%, specificity 65%, area under the receiver operating curve (AUC) 0.68). Tau aggregates were significantly elevated in PSP patients compared to all other groups (sensitivity 87%, specificity 70%, AUC 0.76). Further, we found a tight correlation between aSyn and Tau aggregate titers among all patient cohorts (Pearson coefficient of correlation r = 0.81). Our results demonstrate that aSyn and Tau aggregate concentrations measured by sFIDA differentiate neurodegenerative disease diagnostic groups. Moreover, sFIDA-based Tau aggregate measurements might be particularly useful in distinguishing PSP from other parkinsonisms. Finally, our findings suggest that sFIDA can improve pre-clinical and clinical studies by identifying those individuals that will most likely respond to compounds designed to eliminate specific oligomers or to prevent their formation.
Key findings
- Tau aggregates were significantly elevated in PSP patients compared to all other groups (sensitivity 87%, specificity 70%, AUC 0.76).
- Further, we found a tight correlation between aSyn and Tau aggregate titers among all patient cohorts (Pearson coefficient of correlation r = 0.81).
- Our results demonstrate that aSyn and Tau aggregate concentrations measured by sFIDA differentiate neurodegenerative disease diagnostic groups.
- Finally, our findings suggest that sFIDA can improve pre-clinical and clinical studies by identifying those individuals that will most likely respond to compounds designed to eliminate specific oligomers or to prevent their formation.
Why it matters
Using digital single particle counting, this study found that alpha-synuclein aggregate concentration discriminated Parkinson's disease and dementia with Lewy bodies patients from normal controls, while tau aggregates were significantly elevated in progressive supranuclear palsy patients compared to all other groups. The findings suggest this method can differentiate neurodegenerative disease diagnostic groups and may improve pre-clinical and clinical applications.
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Study details
- Effect sizeAUC 0.76
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (NPJ Parkinson's disease) |
| Journal's citation record | 1 / 4 | Npj Parkinson s Disease: journal h-index 87 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 44 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.3 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 4.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 31 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Dieter Willbold: h-index 58 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35655068) |
| Free to read | 2 / 2 | Free to read |
| Total | 48 / 100 | — |
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Read the original
- DOI: 10.1038/s41531-022-00330-x
- PubMed: 35655068
- Original source →
- Free full text: npj Parkinson s Disease →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Blömeke, L., Pils, M., Kraemer-Schulien, V., Dybala, A., Schaffrath, A., Kulawik, A., et al. (2022). Quantitative detection of α-Synuclein and Tau oligomers and other aggregates by digital single particle counting. NPJ Parkinson's disease. https://doi.org/10.1038/s41531-022-00330-x
Vancouver
Blömeke L, Pils M, Kraemer-Schulien V, Dybala A, Schaffrath A, Kulawik A, et al. Quantitative detection of α-Synuclein and Tau oligomers and other aggregates by digital single particle counting. NPJ Parkinson's disease. 2022. doi:10.1038/s41531-022-00330-x. PMID: 35655068.
BibTeX
@article{blomeke2022-35655068,
author = {Blömeke, L. and Pils, M. and Kraemer-Schulien, V. and Dybala, A. and Schaffrath, A. and Kulawik, A. and Rehn, F. and Cousin, A. and others},
title = {{Quantitative detection of α-Synuclein and Tau oligomers and other aggregates by digital single particle counting}},
journal = {NPJ Parkinson's disease},
year = {2022},
doi = {10.1038/s41531-022-00330-x},
pmid = {35655068},
url = {https://doi.org/10.1038/s41531-022-00330-x}
}
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