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A coordinated and reproducible multicellular response to AD pathology
Vilkaite G, Volcov E, An L, Xiao Y, Hristovska I, Rosat Consiglio C, Pichet-Binette A, Mattsson-Carlgren N et al.. bioRxiv, 2026-10-23
Topic: Genetics and APOE
While single-cell measurements of the Alzheimer’s disease (AD) brain allow investigation of vulnerable cells in unprecedented depth, reported findings are heterogeneous, mostly descriptive and often ignore interdependence of cellular responses. Operationalization of these findings requires a multi-cellular model of AD that is robust and reproducible. Here, we utilize a coordinated multicellular community approach across 2.3 million nuclei from 427 ROSMAP donors to identify robust multicellular axes associated with AD pathology and sex. The AD signature comprised profound alteration to RORB-GABRG excitatory neurons and disrupted oligodendrocyte precursor cell signaling. A separate set of AD-related cell-type specific molecular processes with strong sexual dimorphism also emerged. Importantly, these signatures developed and ROSMAP predicted neuropathology and sex, respectively, in a completely independent dataset (SEA-AD). These findings altogether summarize a highly consistent multi-cellular response to AD pathology in the human brain, creating a baseline cellular model to which perturbation and treatment experiments can be compared.
Key findings
- Operationalization of these findings requires a multi-cellular model of AD that is robust and reproducible.
- Here, we utilize a coordinated multicellular community approach across 2.3 million nuclei from 427 ROSMAP donors to identify robust multicellular axes associated with AD pathology and sex.
- These findings altogether summarize a highly consistent multi-cellular response to AD pathology in the human brain, creating a baseline cellular model to which perturbation and treatment experiments can be compared.
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Preprint — not yet peer-reviewed.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 (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 | 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. |
What each of these 20 components measures, and what this score is not →
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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
Vilkaite, G., Volcov, E., An, L., Xiao, Y., Hristovska, I., Rosat Consiglio, C., et al. (2026). A coordinated and reproducible multicellular response to AD pathology. bioRxiv. https://doi.org/10.64898/2026.10.19.759610
Vancouver
Vilkaite G, Volcov E, An L, Xiao Y, Hristovska I, Rosat Consiglio C, et al. A coordinated and reproducible multicellular response to AD pathology. bioRxiv. 2026. doi:10.64898/2026.10.19.759610.
BibTeX
@article{vilkaite2026-1d27cabc,
author = {Vilkaite, G. and Volcov, E. and An, L. and Xiao, Y. and Hristovska, I. and Rosat Consiglio, C. and Pichet-Binette, A. and Mattsson-Carlgren, N. and others},
title = {{A coordinated and reproducible multicellular response to AD pathology}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.19.759610},
url = {https://doi.org/10.64898/2026.10.19.759610}
}