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Deep nanoparticle protein corona plasma proteomics resolves a stage-specific peripheral signature of Alzheimer’s disease
Mahmoudi N, Ghaffari B, Rogale K, Cheeseman S, Ritz D, Schmidt A, Han L, Li Q et al.. bioRxiv, 2026-07-28
Topic: Disease mechanisms in lab and animal studies
Structured Abstract INTRODUCTION Alzheimer’s disease (AD) progresses over decades, yet plasma biomarkers that resolve disease stage rather than simply detect disease remain scarce. This distinction is clinically consequential because effective AD intervention depends on identifying patients before disease biology has progressed beyond a therapeutically responsive stage. METHODS We used small-molecule-modulated protein corona proteomics to profile plasma from 90 individuals in the Australian Imaging, Biomarker and Lifestyle cohort, stratified by Centiloid (CL) Aβ-amyloid burden (30 amyloid- negative, CL < 15; 30 moderate-to-high, CL 26 to 100; 30 very high, CL > 100). We quantified 3,176 proteins and applied differential abundance and actual causality analyses to identify stage-specific and candidate causal proteins. RESULTS Differential protein abundance was exclusively captured during the moderate-to-high AD transition, revealing a discrete proteomic “switch.” The switch was marked by accumulation of the autophagy receptor CALCOCO1, together with coordinated depletion of the S100A8/S100A9 calprotectin complex and core erythroid-cytoskeletal network structural markers (e.g., SPTA1, SPTB, ANK1). Adhesion G protein-coupled receptor G6 (ADGRG6) showed a significant moderate positive monotonic association with absolute CL burden, providing a proportional molecular anchor for cumulative disease burden. Actual causality analysis identified COL6A2, FOXRED2, P3H1, PRR4, and GOLGA5 as candidate upstream drivers linking matrix remodeling, Golgi trafficking, and collagen processing to AD progression. DISCUSSION These findings suggest a candidate blood-accessible framework for staging AD by active disease biology, which, if replicated in independent cohorts, may have implications for therapeutic selection and mechanism-guided clinical trials. Abstract Figure
Key findings
- RESULTS Differential protein abundance was exclusively captured during the moderate-to-high AD transition, revealing a discrete proteomic “switch.” The switch was marked by accumulation of the autophagy receptor CALCOCO1, together with coordinated depletion of the S100A8/S100A9 calprotectin complex and core erythroid-cytoskeletal network structural markers (e.g., SPTA1, SPTB, ANK1).
- Adhesion G protein-coupled receptor G6 (ADGRG6) showed a significant moderate positive monotonic association with absolute CL burden, providing a proportional molecular anchor for cumulative disease burden.
- DISCUSSION These findings suggest a candidate blood-accessible framework for staging AD by active disease biology, which, if replicated in independent cohorts, may have implications for therapeutic selection and mechanism-guided clinical trials.
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Study details
- Participants90
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 31 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 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 19 of the 62 points we could judge it on, which is 31 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| 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 | 1 / 4 | 90 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 | — / 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 | 19 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 19 of the 62 points we could judge it on is 31 out of 100. |
| Total | 31 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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APA 7th
Mahmoudi, N., Ghaffari, B., Rogale, K., Cheeseman, S., Ritz, D., Schmidt, A., et al. (2026). Deep nanoparticle protein corona plasma proteomics resolves a stage-specific peripheral signature of Alzheimer’s disease. bioRxiv. https://doi.org/10.64898/2026.07.25.740710
Vancouver
Mahmoudi N, Ghaffari B, Rogale K, Cheeseman S, Ritz D, Schmidt A, et al. Deep nanoparticle protein corona plasma proteomics resolves a stage-specific peripheral signature of Alzheimer’s disease. bioRxiv. 2026. doi:10.64898/2026.07.25.740710.
BibTeX
@article{mahmoudi2026-7fb049ee,
author = {Mahmoudi, N. and Ghaffari, B. and Rogale, K. and Cheeseman, S. and Ritz, D. and Schmidt, A. and Han, L. and Li, Q. and others},
title = {{Deep nanoparticle protein corona plasma proteomics resolves a stage-specific peripheral signature of Alzheimer’s disease}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.07.25.740710},
url = {https://doi.org/10.64898/2026.07.25.740710}
}