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Inflammatory biomarker candidates in dementia with Lewy bodies: diagnostic classification, clinical associations, and survival
Pritha A, Swann P, Malpetti M, McKeever A, Mak E, Savulich G, Surendranathan A, Swann O et al.. Research Square, 2026-11-01
Topic: Plasma and spinal-fluid biomarkers
Dementia with Lewy bodies (DLB) is a common neurodegenerative dementia that remains difficult to distinguish clinically from Alzheimer's disease (AD) and related disorders because of overlapping clinical features and frequent mixed pathology. Because alpha-synuclein pathology is associated with central and peripheral immune alterations, targeted measurement of inflammation-related biomarker candidates may provide a minimally invasive means of characterizing disease biology and supporting differential diagnosis. We examined whether plasma concentrations of proteins on the Olink Target 96 Inflammation panel differed between participants with DLB (n = 20), mild cognitive impairment and/or AD (MCI+/AD; n = 15), and cognitively normal controls (n = 15), and assessed their associations with clinical measures and survival. Differential-expression analyses, covariate-adjusted logistic regression with receiver operating characteristic (ROC) analysis, protein-clinical correlations, survival analyses, and pathway enrichment analyses were performed. No protein survived false-discovery-rate correction; nominal associations therefore describe exploratory signals. Relative to controls, DLB showed nominally higher CCL20 and CXCL11. Compared with MCI+/AD, DLB showed nominally lower MCP-2 and IL-2 and higher IL-18R1, TRANCE, GDNF, and IL-12B. AUCs derived from multivariable logistic models containing each protein and prespecified covariates ranged from 0.853 to 0.890 for the DLB versus MCI+/AD comparison. Higher TRANCE was nominally associated with greater motor severity (UPDRS: rho = 0.41, p = 0.0176), whereas its associations with ACE-R and MMSE did not reach nominal significance. Survival analyses identified limited and imprecise associations over a median follow-up of 6.5 years (range 0.07–9.80; IQR 3.49–7.93 years). Pathway analyses highlighted immune and intracellular signaling networks, including NF-kB and MAPK signaling. These exploratory findings support a targeted peripheral inflammatory signature in DLB that differs from normal ageing and MCI+/AD but require validation in larger independent cohorts.
Key findings
- Because alpha-synuclein pathology is associated with central and peripheral immune alterations, targeted measurement of inflammation-related biomarker candidates may provide a minimally invasive means of characterizing disease biology and supporting differential diagnosis.
- Compared with MCI+/AD, DLB showed nominally lower MCP-2 and IL-2 and higher IL-18R1, TRANCE, GDNF, and IL-12B.
- AUCs derived from multivariable logistic models containing each protein and prespecified covariates ranged from 0.853 to 0.890 for the DLB versus MCI+/AD comparison.
- Higher TRANCE was nominally associated with greater motor severity (UPDRS: rho = 0.41, p = 0.0176), whereas its associations with ACE-R and MMSE did not reach nominal significance.
Study details
- Participants20
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 27 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 17 of the 62 points we could judge it on, which is 27 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| 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 | 1 / 4 | 20 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 | 17 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 17 of the 62 points we could judge it on is 27 out of 100. |
| Total | 27 / 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
Pritha, A., Swann, P., Malpetti, M., McKeever, A., Mak, E., Savulich, G., et al. (2026). Inflammatory biomarker candidates in dementia with Lewy bodies: diagnostic classification, clinical associations, and survival. Research Square. https://doi.org/10.21203/rs.3.rs-11368506/v1
Vancouver
Pritha A, Swann P, Malpetti M, McKeever A, Mak E, Savulich G, et al. Inflammatory biomarker candidates in dementia with Lewy bodies: diagnostic classification, clinical associations, and survival. Research Square. 2026. doi:10.21203/rs.3.rs-11368506/v1.
BibTeX
@article{pritha2026-532af7a3,
author = {Pritha, A. and Swann, P. and Malpetti, M. and McKeever, A. and Mak, E. and Savulich, G. and Surendranathan, A. and Swann, O. and others},
title = {{Inflammatory biomarker candidates in dementia with Lewy bodies: diagnostic classification, clinical associations, and survival}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-11368506/v1},
url = {https://doi.org/10.21203/rs.3.rs-11368506/v1}
}