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CSF Alzheimer’s Disease Biomarkers in Relation to Functional Status and Tofersen Treatment Response in ALS
Eberle F, Bernsen S, Rachel F, Widmann C, Weydt P, Castro-Gomez S.. medRxiv, 2026-10-28
Topic: Plasma and spinal-fluid biomarkers
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily affecting motor neurons but also frequently involving cognitive impairment. Cerebrospinal fluid (CSF) measurements of β-amyloid peptides (Aβ 40 , Aβ 42 ), tau proteins, and neurofilaments are clinically established biomarkers in neurodegenerative disorders such as Alzheimer’s disease (AD). Emerging evidence suggests that AD-related pathological changes and AD-related biomarkers may appear in ALS, yet their diagnostic and prognostic significance remains unclear. In this retrospective study, we analyzed clinical and CSF biomarker data from patients with ALS, AD, Huntington’s disease (HD), and other disease controls recruited in real-world clinical settings. The dataset comprised Aβ 40 , Aβ 42 , total tau (t-Tau), phosphorylated tau181 (pTau181), phosphorylated neurofilament heavy chain (pNfH), and relevant serum markers. Additionally, longitudinal CSF sampling over one year was evaluated in three ALS patients receiving tofersen treatment. In this real-world cohort, AD-related CSF biomarkers demonstrated no diagnostic value for distinguishing ALS from other neurodegenerative conditions. However, Aβ 40 , Aβ 42 , and pTau181 levels correlated positively with ALS Functional Rating Scale (ALSFRS-R) global score and serum Creatine Kinase MB (CK-MB) concentrations. At the same time, a higher Aβ 42 /Aβ 40 ratio was associated with better memory performance on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). In tofersen-treated cases, AD-related biomarkers gradually declined during follow-up. These findings suggest that elevated CSF AD–associated biomarkers in ALS may reflect preserved functional and cognitive status and exhibited parallel declines during follow-up in three tofersen-treated patients, supporting their further prospective evaluation as exploratory markers of therapeutic responsiveness. Graphical Abstract Pending
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APA 7th
Eberle, F., Bernsen, S., Rachel, F., Widmann, C., Weydt, P., & Castro-Gomez, S. (2026). CSF Alzheimer’s Disease Biomarkers in Relation to Functional Status and Tofersen Treatment Response in ALS. medRxiv. https://doi.org/10.64898/2026.10.26.26366525
Vancouver
Eberle F, Bernsen S, Rachel F, Widmann C, Weydt P, Castro-Gomez S. CSF Alzheimer’s Disease Biomarkers in Relation to Functional Status and Tofersen Treatment Response in ALS. medRxiv. 2026. doi:10.64898/2026.10.26.26366525.
BibTeX
@article{eberle2026-65085d45,
author = {Eberle, F. and Bernsen, S. and Rachel, F. and Widmann, C. and Weydt, P. and Castro-Gomez, S.},
title = {{CSF Alzheimer’s Disease Biomarkers in Relation to Functional Status and Tofersen Treatment Response in ALS}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.10.26.26366525},
url = {https://doi.org/10.64898/2026.10.26.26366525}
}
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Key findings
- Emerging evidence suggests that AD-related pathological changes and AD-related biomarkers may appear in ALS, yet their diagnostic and prognostic significance remains unclear.
- In this real-world cohort, AD-related CSF biomarkers demonstrated no diagnostic value for distinguishing ALS from other neurodegenerative conditions.
- At the same time, a higher Aβ 42 /Aβ 40 ratio was associated with better memory performance on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS).
- These findings suggest that elevated CSF AD–associated biomarkers in ALS may reflect preserved functional and cognitive status and exhibited parallel declines during follow-up in three tofersen-treated patients, supporting their further prospective evaluation as exploratory markers of therapeutic responsiveness.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 35 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 22 of the 62 points we could judge it on, which is 35 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| 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 | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 22 of the 62 points we could judge it on is 35 out of 100. |
| Total | 35 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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