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Abnormalities in core AD biomarkers precede inflammatory and glial markers in CSF in Autosomal Dominant Alzheimer’s Disease
Lin W, Beric A, Wisch JK, Baker B, Jerome G, Minton M, Preminger S, Stauber J et al.. medRxiv, 2026-04-01
Topic: Amyloid, tau and blood-test diagnosis
ABSTRACT BACKGROUND Increasing evidence suggests that accurate prediction of Alzheimer’s disease (AD) symptom onset requires more than amyloid- and tau-centric biomarkers such as cerebrospinal fluid (CSF) Aβ42/40, total tau and p-tau181 and plasma p-tau217. Autosomal dominant AD (ADAD), caused by pathogenic PSEN1, PSEN2 and APP mutations with predictable age at symptom onset, presents a unique opportunity to characterize the chronological changes in proteins beyond amyloid and tau and clarify them as early biomarkers of disease onset or as biomarkers related to disease staging and progression monitoring. METHODS We measured 972 CSF samples corresponding to 484 participants of the Dominantly Inherited Alzheimer Disease Network (DIAN) using the NULISASeq 120 CNS Disease Panel.
Key findings
- Autosomal dominant AD (ADAD), caused by pathogenic PSEN1, PSEN2 and APP mutations with predictable age at symptom onset, presents a unique opportunity to characterize the chronological changes in proteins beyond amyloid and tau and clarify them as early biomarkers of disease onset or as biomarkers related to disease staging and progression monitoring.
- METHODS We measured 972 CSF samples corresponding to 484 participants of the Dominantly Inherited Alzheimer Disease Network (DIAN) using the NULISASeq 120 CNS Disease Panel.
- We first benchmarked the technology against gold-standard measurements followed by the identification of proteins that were differentially abundant in relation to mutation status and symptomatology.
- Next, we determined the chronological emergence of protein changes in relation to the estimated years to onset (EYO).
Why it matters
Using 972 cerebrospinal fluid samples from 484 participants in the Dominantly Inherited Alzheimer Disease Network, this study found that core Alzheimer's disease biomarker abnormalities precede inflammatory and glial markers in autosomal dominant Alzheimer's disease. It clarifies the order of biomarker changes and does not test treatment, cure, or prevention.
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Study details
- Participants484
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 28 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 26 of the 94 points we could judge it on, which is 28 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 | 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 | 2 / 4 | 484 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 | 2 / 4 | Last-listed author Laura Ibáñez: h-index 37 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 27 institution(s) in 8 countries |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 26 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 26 of the 94 points we could judge it on is 28 out of 100. |
| Total | 28 / 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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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
Lin, W., Beric, A., Wisch, J. K., Baker, B., Jerome, G., Minton, M., et al. (2026). Abnormalities in core AD biomarkers precede inflammatory and glial markers in CSF in Autosomal Dominant Alzheimer’s Disease. medRxiv. https://doi.org/10.64898/2026.03.31.26349851
Vancouver
Lin W, Beric A, Wisch JK, Baker B, Jerome G, Minton M, et al. Abnormalities in core AD biomarkers precede inflammatory and glial markers in CSF in Autosomal Dominant Alzheimer’s Disease. medRxiv. 2026. doi:10.64898/2026.03.31.26349851.
BibTeX
@article{lin2026-2a0fe361,
author = {Lin, W. and Beric, A. and Wisch, J. K. and Baker, B. and Jerome, G. and Minton, M. and Preminger, S. and Stauber, J. and others},
title = {{Abnormalities in core AD biomarkers precede inflammatory and glial markers in CSF in Autosomal Dominant Alzheimer’s Disease}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.03.31.26349851},
url = {https://doi.org/10.64898/2026.03.31.26349851}
}
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