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Big tau and brain-derived tau reveal peripheral and central nervous system involvement in neuropathies
Martin-Aguilar, L.; Gonzalez-Ortiz, F.; Zetterberg, H.; Karikari, T. K.; Suarez-Calvet, M.; Casasnovas, C.; Gutierrez-Gutierrez, G.; Sedano-Tous et al.. medRxiv (preprint), 2026-08-31
Topic: Brain proteins, microglia and lab models
INTRODUCTIONBiomarkers for monitoring disease activity and treatment response in peripheral neuropathies remain limited. Big tau, a high-molecular-weight isoform of tau, is predominantly expressed in the peripheral nervous system (PNS). We investigated serum levels of big tau, brain-derived tau (BD-tau), and neurofilament light chain (NfL) in peripheral neuropathies, multiple sclerosis (MS), Alzheimers disease (AD), and healthy controls (HC). METHODSUltra-sensitive blood-based assays run on an HD-X Single Molecule Array analyser (Quanterix) were used to measure big tau and BD-tau in serum from patients with Guillain-Barre syndrome (GBS, n=81), Miller Fisher syndrome (MFS, n=20), Charcot-Marie-Tooth disease (CMT, n=102), chronic inflammatory demyelinating polyneuropathy (CIDP, n=43), MS (n=159), AD (n=20), and HC (n=41). NfL was measured in patients with neuropathies using an SR-X Single Molecule Array analyser (Quanterix). RESULTSSerum big tau levels were higher in GBS than in AD (11.4 vs 2.4 pg/mL, p<0.0001) and MS (11.4 vs 9.0 pg/mL, p=0.01), and similar to CIDP and CMT. Contrarily, serum BD-tau levels in GBS were higher than in CIDP (3.0 vs 2.3 pg/mL, p=0.006) and MS (3.0 vs 1.7 pg/mL, p<0.0001), but similar to CMT, and lower than in AD (3.0 vs 9.8 pg/mL, p<0.0001). Serum NfL levels were higher in GBS than in CIDP (32.5 vs 13.0 pg/mL, p=0.0002), CMT (32.5 vs 12.3 pg/mL, p<0.0001), and HC (32.5 vs 7.6 pg/mL, p<0.0001). Compared with GBS, MFS patients showed higher BD-tau (12.7 vs 3.0 pg/mL, p=0.003), lower big tau (5.4 vs 11.4 pg/mL, p=0.002), and higher NfL levels, although the latter did not reach statistical significance (118.3 vs 32.5 pg/mL, p=0.16). The NfL/big tau ratio was significantly higher in MFS than in GBS, CIDP, and CMT. In GBS, BD-tau correlated with early clinical severity (MRC at 1 week; I-RODS at 4 weeks; maximum GBS-DS and GBS-DS at 4 weeks), whereas neither tau biomarker showed long-term clinical correlations. Higher BD-tau and big tau levels were associated with the need for mechanical ventilation (BD-tau: 8.6 vs 2.9 pg/mL, p=0.019; big tau: 19.7 vs 10.7 pg/mL, p=0.007), while higher BD-tau levels were associated with mortality (10.9 vs 2.9 pg/mL, p=0.003). CONCLUSIONSHigher big tau levels in peripheral neuropathies than in CNS diseases support its role as a PNS-specific biomarker. In MFS, increased serum BD-tau, reduced big tau, and an elevated NfL/big tau ratio suggest CNS involvement with relative preservation of the PNS.
Key findings
- Compared with GBS, MFS patients showed higher BD-tau (12.7 vs 3.0 pg/mL, p=0.003), lower big tau (5.4 vs 11.4 pg/mL, p=0.002), and higher NfL levels, although the latter did not reach statistical significance (118.3 vs 32.5 pg/mL, p=0.16).
- The NfL/big tau ratio was significantly higher in MFS than in GBS, CIDP, and CMT.
- Higher BD-tau and big tau levels were associated with the need for mechanical ventilation (BD-tau: 8.6 vs 2.9 pg/mL, p=0.019; big tau: 19.7 vs 10.7 pg/mL, p=0.007), while higher BD-tau levels were associated with mortality (10.9 vs 2.9 pg/mL, p=0.003).
Why it matters
This study measured blood levels of big tau, brain-derived tau and neurofilament light chain in people with nerve disorders, multiple sclerosis, Alzheimer's disease and healthy controls. It is about biomarkers for peripheral neuropathies and does not test any treatment, cure or prevention for Alzheimer's disease.
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Study details
- Participants81
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 29 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 27 of the 94 points we could judge it on, which is 29 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv (preprint)) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 1 / 4 | 81 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Luís Querol: h-index 53 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 30 institution(s) in 4 countries |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 27 of the 94 points we could judge it on is 29 out of 100. |
| Total | 29 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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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
Martin-Aguilar, L., Gonzalez-Ortiz, F., Zetterberg, H., Karikari, T. K., Suarez-Calvet, M., Casasnovas, C., et al. (2026). Big tau and brain-derived tau reveal peripheral and central nervous system involvement in neuropathies. medRxiv (preprint). https://doi.org/10.64898/2026.08.27.26361202
Vancouver
Martin-Aguilar L, Gonzalez-Ortiz F, Zetterberg H, Karikari TK, Suarez-Calvet M, Casasnovas C, et al. Big tau and brain-derived tau reveal peripheral and central nervous system involvement in neuropathies. medRxiv (preprint). 2026. doi:10.64898/2026.08.27.26361202.
BibTeX
@article{martinaguilar2026-a46fba4d,
author = {Martin-Aguilar, L. and Gonzalez-Ortiz, F. and Zetterberg, H. and Karikari, T. K. and Suarez-Calvet, M. and Casasnovas, C. and Gutierrez-Gutierrez, G. and Sedano-Tous and others},
title = {{Big tau and brain-derived tau reveal peripheral and central nervous system involvement in neuropathies}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.08.27.26361202},
url = {https://doi.org/10.64898/2026.08.27.26361202}
}
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