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Physiological variability in key Alzheimer's biomarkers in amyloid-positive clinical trial cohorts and the mechanistic basis of biomarker ratios
Tasiudi, E.; Hawellek, D. J.; Aponte, E.; Tonietto, M.; Soares, H.; Diack, C.; Soubret, A.; Kam-Thong et al.. medRxiv (preprint), 2026-09-21
Topic: Amyloid, tau and blood-test diagnosis
While normalizing biomarker values by A{beta}40 or A{beta}42 reduced physiological variability for some biomarkers, the effects of the normalization were compartment-, and cohort-dependent. Using our framework, we identified two conditions under which ratio-based normalization is most likely to improve biomarker performance: (1) the target and reference biomarkers strongly share physiological variability, and (2) they maintain independent neurobiological variability. These conditions provide a mechanistic explanation for why A{beta}-based ratios are useful for some biomarkers but are not optimal for others. DiscussionThese findings advance our understanding of the sources of biomarker variability in clinical trials and provide a framework for better understanding the mechanistic basis of ratio-based normalization. This work aims to strengthen the utility of using biomarkers by clarifying when and why ratio-based approaches are most informative.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Tasiudi, E., Hawellek, D. J., Aponte, E., Tonietto, M., Soares, H., Diack, C., et al. (2026). Physiological variability in key Alzheimer's biomarkers in amyloid-positive clinical trial cohorts and the mechanistic basis of biomarker ratios. medRxiv (preprint). https://doi.org/10.64898/2026.09.18.26363412
Vancouver
Tasiudi E, Hawellek DJ, Aponte E, Tonietto M, Soares H, Diack C, et al. Physiological variability in key Alzheimer's biomarkers in amyloid-positive clinical trial cohorts and the mechanistic basis of biomarker ratios. medRxiv (preprint). 2026. doi:10.64898/2026.09.18.26363412.
BibTeX
@article{tasiudi2026-281c7577,
author = {Tasiudi, E. and Hawellek, D. J. and Aponte, E. and Tonietto, M. and Soares, H. and Diack, C. and Soubret, A. and Kam-Thong and others},
title = {{Physiological variability in key Alzheimer's biomarkers in amyloid-positive clinical trial cohorts and the mechanistic basis of biomarker ratios}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.09.18.26363412},
url = {https://doi.org/10.64898/2026.09.18.26363412}
}
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
- While normalizing biomarker values by A{beta}40 or A{beta}42 reduced physiological variability for some biomarkers, the effects of the normalization were compartment-, and cohort-dependent.
- Using our framework, we identified two conditions under which ratio-based normalization is most likely to improve biomarker performance: (1) the target and reference biomarkers strongly share physiological variability, and (2) they maintain independent neurobiological variability.
- These conditions provide a mechanistic explanation for why A{beta}-based ratios are useful for some biomarkers but are not optimal for others.
- DiscussionThese findings advance our understanding of the sources of biomarker variability in clinical trials and provide a framework for better understanding the mechanistic basis of ratio-based normalization.
- This work aims to strengthen the utility of using biomarkers by clarifying when and why ratio-based approaches are most informative.
Why it matters
This analysis explains when and why normalizing Alzheimer's biomarker values by dividing them by another biomarker is likely to improve their usefulness. It is methodological work to strengthen biomarker interpretation in trials, not a study of any treatment or prevention.
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Study details
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 19 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people 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 18 of the 94 points we could judge it on, which is 19 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 | 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 | 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 | 1 / 4 | Last-listed author Marcelo Boareto: h-index 15 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Roche (Switzerland): institution h-index 638 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 18 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 18 of the 94 points we could judge it on is 19 out of 100. |
| Total | 19 / 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 →
Read the original
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