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Biomarker-informed CSF proteomics reveals ENPP2–LPA lipid signaling associated with Alzheimer’s disease
Qiao M, Bhattarai P, Yilmaz E, Rookyard AW, Das L, Jain A, Reyes-Dumeyer D, Lee AJ et al.. medRxiv, 2026-07-10
Topic: Inflammation, microglia and astrocytes
We validated results in CSF from 397 participants in the Accelerated Medicine Partnership-Alzheimer’s Disease cohort. Results We detected 1030 proteins, yielding an overall data completeness value of 97%. CSF levels of 75 (7.3%) proteins were significantly associated with CSF P-tau181 levels after multiple testing correction. These proteins were also associated with CSF Aβ42/Aβ40 ratio and total tau levels but not with NfL. OPN was also associated with CSF levels of GFAP (p=1.32e-05). Among proteins associated with P-tau181 levels, pathways related to axon development (p=2.4E-12), axonogenesis (p=1.45E-11) and regulation of axonogenesis (p=5.1E-09) were enriched. Immunostaining on postmortem human and zebrafish brain found that ENPP2 expression, the gene encoding ATX, was significantly reduced in AD brain and in the amyloidosis model in zebrafish. One sentence summary Reduced autotaxin and lysophosphatidic acid were among 75 cerebrospinal fluid (CSF) proteins associated with biomarker-defined Alzheimer’s disease pathology.
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APA 7th
Qiao, M., Bhattarai, P., Yilmaz, E., Rookyard, A. W., Das, L., Jain, A., et al. (2026). Biomarker-informed CSF proteomics reveals ENPP2–LPA lipid signaling associated with Alzheimer’s disease. medRxiv. https://doi.org/10.64898/2026.07.08.26357565
Vancouver
Qiao M, Bhattarai P, Yilmaz E, Rookyard AW, Das L, Jain A, et al. Biomarker-informed CSF proteomics reveals ENPP2–LPA lipid signaling associated with Alzheimer’s disease. medRxiv. 2026. doi:10.64898/2026.07.08.26357565.
BibTeX
@article{qiao2026-7155c963,
author = {Qiao, M. and Bhattarai, P. and Yilmaz, E. and Rookyard, A. W. and Das, L. and Jain, A. and Reyes-Dumeyer, D. and Lee, A. J. and others},
title = {{Biomarker-informed CSF proteomics reveals ENPP2–LPA lipid signaling associated with Alzheimer’s disease}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.07.08.26357565},
url = {https://doi.org/10.64898/2026.07.08.26357565}
}
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Key findings
- We validated results in CSF from 397 participants in the Accelerated Medicine Partnership-Alzheimer’s Disease cohort.
- Results We detected 1030 proteins, yielding an overall data completeness value of 97%.
- CSF levels of 75 (7.3%) proteins were significantly associated with CSF P-tau181 levels after multiple testing correction.
- These proteins were also associated with CSF Aβ42/Aβ40 ratio and total tau levels but not with NfL.
- OPN was also associated with CSF levels of GFAP (p=1.32e-05).
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Study details
- Participants500
- Effect size7.3%
- 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 study design 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 | 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 | 2 / 4 | 500 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | — / 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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