Proteogenomics captures a midlife biological state of Alzheimer’s disease susceptibility
Perry AS, Adegboye HA, Bledsoe X, Archer D, Tiwari A, Lin P, Farber-Eger E, Perera BLA et al.. medRxiv, 2026-10-26
Topic: Genetics and APOE
Alzheimer’s disease (AD) develops over decades, but biological processes underlying susceptibility during midlife remain poorly understood. Using multimodal neuroimaging and plasma proteomics in UK Biobank participants, we identified circulating proteomic signatures of brain structure and organization. This ‘neurostructural proteome’ predicted future cognitive decline, incident dementia, and later-life AD pathology across independent cohorts spanning two decades of follow-up. Genetic and single-nucleus transcriptomic analyses demonstrated convergence of the neurostructural proteome and AD genetic architecture, highlighting enrichment in astrocyte, microglia, and endothelial pathways beyond the APOE region. Collectively, these findings identify a circulating neurostructural proteome detectable in midlife that captures molecular processes associated with future AD susceptibility and provide a framework for uncovering an early biological landscape of disease susceptibility that precedes conventional biomarkers and clinical onset.
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APA 7th
Perry, A. S., Adegboye, H. A., Bledsoe, X., Archer, D., Tiwari, A., Lin, P., et al. (2026). Proteogenomics captures a midlife biological state of Alzheimer’s disease susceptibility. medRxiv. https://doi.org/10.64898/2026.10.22.26366029
Vancouver
Perry AS, Adegboye HA, Bledsoe X, Archer D, Tiwari A, Lin P, et al. Proteogenomics captures a midlife biological state of Alzheimer’s disease susceptibility. medRxiv. 2026. doi:10.64898/2026.10.22.26366029.
BibTeX
@article{perry2026-2e952610,
author = {Perry, A. S. and Adegboye, H. A. and Bledsoe, X. and Archer, D. and Tiwari, A. and Lin, P. and Farber-Eger, E. and Perera, B. L. A. and others},
title = {{Proteogenomics captures a midlife biological state of Alzheimer’s disease susceptibility}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.10.22.26366029},
url = {https://doi.org/10.64898/2026.10.22.26366029}
}
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Key findings
- Genetic and single-nucleus transcriptomic analyses demonstrated convergence of the neurostructural proteome and AD genetic architecture, highlighting enrichment in astrocyte, microglia, and endothelial pathways beyond the APOE region.
- Collectively, these findings identify a circulating neurostructural proteome detectable in midlife that captures molecular processes associated with future AD susceptibility and provide a framework for uncovering an early biological landscape of disease susceptibility that precedes conventional biomarkers and clinical onset.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 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 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 13 of the 62 points we could judge it on, which is 21 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 | 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 | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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