Alzheimer’s Disease-Associated Proteomic Changes in Olfactory Stem Cells Show Pathway-Level Transcriptomic Overlap
Rantanen LM, Robinson H, Dutra Voigt D, Diaz X, Lampinen R, Mykkänen S, Kalapudas J, Koivisto AM et al.. bioRxiv, 2026-10-24
Topic: Gut, metabolism and diet
Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder and the leading cause of dementia worldwide. Although recent therapeutic advances have provided some disease-modifying potential, there is currently no curative treatment for AD, highlighting the need for improved disease models and early biomarkers. Olfactory mucosal stem cells, which can be expanded in vitro as olfactory neurosphere-derived (ONS) cells, represent a promising source for biomarker discovery because olfactory tissue is more accessible than central nervous system tissue and has been reported to exhibit AD-related pathological changes. In this study, we used subcellular fractionation-based proteomics, reconstructed bulk proteomics and integrated transcriptomic-proteomic analyses to characterise alterations in ONS cells derived from healthy control, mild cognitive impairment (MCI) and AD individuals. Fraction-specific proteomics identified cytoplasmic and nuclear-enriched protein abundance changes, including alterations in proteins and pathways associated with cytoskeletal organisation, RNA processing, intracellular trafficking, autophagy and mitochondrial/metabolic processes. Reduced LC3B abundance in cytoplasmic AD ONS cells was supported by western blot analysis, although LC3B abundance alone does not indicate altered autophagic flux. Reconstructed bulk proteomics identified 40 FDR-significant proteins in AD compared with HC, defining an AD-associated protein signature enriched for extracellular matrix, cytoskeletal, organelle-associated and RNA-processing pathways. Despite proteomic enrichment of mitochondrial and metabolic pathways, Seahorse Mito Stress Test analysis did not identify significant group-level differences in mitochondrial respiration. Integrated transcriptomic-proteomic analysis revealed partial RNA-protein concordance and pathway-level overlap across disease-associated processes. Together, these findings support the use of patient-derived ONS cells as a model for investigating AD- and MCI-associated molecular changes and highlight protein signatures for further validation.
Key findings
- Fraction-specific proteomics identified cytoplasmic and nuclear-enriched protein abundance changes, including alterations in proteins and pathways associated with cytoskeletal organisation, RNA processing, intracellular trafficking, autophagy and mitochondrial/metabolic processes.
- Reconstructed bulk proteomics identified 40 FDR-significant proteins in AD compared with HC, defining an AD-associated protein signature enriched for extracellular matrix, cytoskeletal, organelle-associated and RNA-processing pathways.
- Despite proteomic enrichment of mitochondrial and metabolic pathways, Seahorse Mito Stress Test analysis did not identify significant group-level differences in mitochondrial respiration.
- Integrated transcriptomic-proteomic analysis revealed partial RNA-protein concordance and pathway-level overlap across disease-associated processes.
- Together, these findings support the use of patient-derived ONS cells as a model for investigating AD- and MCI-associated molecular changes and highlight protein signatures for further validation.
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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 (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. |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Rantanen, L. M., Robinson, H., Dutra Voigt, D., Diaz, X., Lampinen, R., Mykkänen, S., et al. (2026). Alzheimer’s Disease-Associated Proteomic Changes in Olfactory Stem Cells Show Pathway-Level Transcriptomic Overlap. bioRxiv. https://doi.org/10.64898/2026.10.19.760270
Vancouver
Rantanen LM, Robinson H, Dutra Voigt D, Diaz X, Lampinen R, Mykkänen S, et al. Alzheimer’s Disease-Associated Proteomic Changes in Olfactory Stem Cells Show Pathway-Level Transcriptomic Overlap. bioRxiv. 2026. doi:10.64898/2026.10.19.760270.
BibTeX
@article{rantanen2026-b5739013,
author = {Rantanen, L. M. and Robinson, H. and Dutra Voigt, D. and Diaz, X. and Lampinen, R. and Mykkänen, S. and Kalapudas, J. and Koivisto, A. M. and others},
title = {{Alzheimer’s Disease-Associated Proteomic Changes in Olfactory Stem Cells Show Pathway-Level Transcriptomic Overlap}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.19.760270},
url = {https://doi.org/10.64898/2026.10.19.760270}
}
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