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Novel immunoassays for TDP‐43 detection in plasma and CSF
Catherine Demos, Nikhil Padmanabhan, Sree Uttarala, Leonid Dzantiev, James Berry, Anu Mathew, Martin K. Stengelin, George B. Sigal et al.. Alzheimer s & Dementia, 2025-12-01
Topic: Brain proteins, microglia and lab models
The full length TDP-43 assay in standard format had a quantitative range of 10-275,000 pg/mL and sufficient sensitivity to quantitate 100% of the tested plasma samples. The assay displayed excellent dilution linearity. Whole blood, plasma and platelet-rich plasma show higher concentrations than red blood cells, serum and platelet-poor plasma, suggesting a need for good control over efficiency and timing of the separation of plasma from platelets and blood cells to avoid pre-analytical effects. To measure the lower TDP-43 levels in CSF samples, the more sensitive S-PLEX TDP-43 assay was used. It had a quantitative range of 5-34,000 pg/mL and was able to quantitate 48% of the tested CSF samples. The S-PLEX pTDP-43 assay was used to measure TDP-43 phosphorylated at S409/410 in plasma samples. It had a quantitative range of 1-50,000 pg/mL, and was able to quantitate 100% of the tested plasma samples. Specificity was confirmed by testing phosphorylated and non-phosphorylated purified protein. To preliminarily evaluate the assays, a small set of plasma and CSF samples from individuals with ALS was tested. Relative to the control samples, the ALS samples had higher median plasma TDP-43 levels (ratio = 4.8, p = 0.0018), lower median CSF TDP-43 levels (ratio = 0.49, p = 0.01), and non-significantly higher plasma pTDP-43 levels (ratio = 1.9, p = 0.11). Newly developed immunoassays for TDP-43 and pTDP-43 provide powerful tools for research on neurodegeneration biomarkers.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Demos, C., Padmanabhan, N., Uttarala, S., Dzantiev, L., Berry, J., Mathew, A., et al. (2025). Novel immunoassays for TDP‐43 detection in plasma and CSF. Alzheimer s & Dementia. https://doi.org/10.1002/alz70856_098094
Vancouver
Demos C, Padmanabhan N, Uttarala S, Dzantiev L, Berry J, Mathew A, et al. Novel immunoassays for TDP‐43 detection in plasma and CSF. Alzheimer s & Dementia. 2025. doi:10.1002/alz70856_098094. PMID: 41443670.
BibTeX
@article{demos2025-41443670,
author = {Demos, Catherine and Padmanabhan, Nikhil and Uttarala, Sree and Dzantiev, Leonid and Berry, James and Mathew, Anu and Stengelin, Martin K. and Sigal, George B. and others},
title = {{Novel immunoassays for TDP‐43 detection in plasma and CSF}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70856_098094},
pmid = {41443670},
url = {https://doi.org/10.1002/alz70856_098094}
}
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.
Key findings
- The full length TDP-43 assay in standard format had a quantitative range of 10-275,000 pg/mL and sufficient sensitivity to quantitate 100% of the tested plasma samples.
- The assay displayed excellent dilution linearity.
- Whole blood, plasma and platelet-rich plasma show higher concentrations than red blood cells, serum and platelet-poor plasma, suggesting a need for good control over efficiency and timing of the separation of plasma from platelets and blood cells to avoid pre-analytical effects.
- To measure the lower TDP-43 levels in CSF samples, the more sensitive S-PLEX TDP-43 assay was used.
- It had a quantitative range of 5-34,000 pg/mL and was able to quantitate 48% of the tested CSF samples.
Why it matters
This study developed new immunoassays to detect TDP-43 in plasma and cerebrospinal fluid, and in a small set of samples found higher median plasma TDP-43 and lower median CSF TDP-43 in people with ALS compared with controls, while plasma pTDP-43 was non-significantly higher. These are preliminary assay-development findings and no treatment, cure or prevention is tested.
Study details
- Evidence strengthLow
How this study scored 34/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, 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 (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 4 / 5 | 2025 — within 3 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 | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 1 / 6 | Cited 0.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Jacob N. Wohlstadter: h-index 10 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Massachusetts General Hospital: institution h-index 2,057 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41443670) |
| Free to read | 2 / 2 | Free to read |
| Total | 34 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/alz70856_098094
- PubMed: 41443670
- Original source →
- Free full text: Alzheimer s & Dementia →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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