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Neuroinflammation is an early pathological process in a mouse model of prodromal Parkinsons disease
Mercado G, Stetzik L, Schulz E, Meyerdirk L, Lindquist A, Cohen L, Escobar Galvis ML, Steiner JA et al.. bioRxiv, 2026-10-30
Topic: Inflammation, microglia and astrocytes
Approximately 90% of Parkinson's disease (PD) patients exhibit olfactory deficits, which often precedes motor symptoms by years, and are a robust predictor for PD and subsequent cognitive decline. Pathological changes in the PD olfactory system, particularly αsynuclein (αSyn) pathology in the olfactory bulb (OB) and severe involvement of the anterior olfactory nucleus (AON), are distinct from normal aging. However, the causal link between αSyn aggregation and functional impairment, potentially involving cytotoxicity and neuroinflammation, remains elusive. To investigate these early pathological events, we utilized a prodromal PD model that we have previously characterized, involving the unilateral OB injection of αSyn preformed fibrils (PFF) in wild–type mice. This triggers the transneuronal spread of pathogenic αSyn, and olfactory dysfunction starting at 1–month post-injections. Here we report on neuropathological and inflammatory events 1–3 month following injection of PFFs into the OB. Following PFF injection, αSyn pSer129 pathology progressively accumulated bilaterally in the AON and ipsilateral in the piriform cortex (PCX) over three months. Stereological quantification revealed no significant neuronal loss in the AON or PCX during this 1–3 month interval, indicating that olfactory impairment precedes overt neurodegeneration. Instead, we identified the upregulation of pro-inflammatory genes (Il-1β ; and Il-6), significant microglial reactivity, and sustained astrogliosis within olfactory structures. These findings identify neuroinflammation as a key early mediator linking αSyn pathology to olfactory dysfunction in the absence of neuronal loss. This suggests a critical window for therapeutic intervention and highlights neuroinflammatory markers as potential biomarkers for the prodromal phase of PD.
Key findings
- Stereological quantification revealed no significant neuronal loss in the AON or PCX during this 1–3 month interval, indicating that olfactory impairment precedes overt neurodegeneration.
- Instead, we identified the upregulation of pro-inflammatory genes (Il-1β ; and Il-6), significant microglial reactivity, and sustained astrogliosis within olfactory structures.
- These findings identify neuroinflammation as a key early mediator linking αSyn pathology to olfactory dysfunction in the absence of neuronal loss.
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 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 | Laboratory or animal study (title names “mouse”) — scores zero |
| 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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APA 7th
Mercado, G., Stetzik, L., Schulz, E., Meyerdirk, L., Lindquist, A., Cohen, L., et al. (2026). Neuroinflammation is an early pathological process in a mouse model of prodromal Parkinsons disease. bioRxiv. https://doi.org/10.64898/2026.10.29.762888
Vancouver
Mercado G, Stetzik L, Schulz E, Meyerdirk L, Lindquist A, Cohen L, et al. Neuroinflammation is an early pathological process in a mouse model of prodromal Parkinsons disease. bioRxiv. 2026. doi:10.64898/2026.10.29.762888.
BibTeX
@article{mercado2026-398d9a8d,
author = {Mercado, G. and Stetzik, L. and Schulz, E. and Meyerdirk, L. and Lindquist, A. and Cohen, L. and Escobar Galvis, M. L. and Steiner, J. A. and others},
title = {{Neuroinflammation is an early pathological process in a mouse model of prodromal Parkinsons disease}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.29.762888},
url = {https://doi.org/10.64898/2026.10.29.762888}
}