Inflammatory biomarker candidates in dementia with Lewy bodies: diagnostic classification, clinical associations, and survival
Abstract
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.
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BibTeX
@misc{pritha2026inflammatory,
title = {{Inflammatory biomarker candidates in dementia with Lewy bodies: diagnostic classification, clinical associations, and survival}},
author = {Ariana Pritha and Peter Swann and Maura Malpetti and Anna McKeever and Elijah Mak and George Savulich and Ajenthan Surendranathan and Owen Swann and Amanda Heslegrave and Henrik Zetterberg and James B. Rowe and Leonidas Chouliaras and John T. O'Brien},
howpublished = {Research Square},
year = {2026},
month = nov,
doi = {10.21203/rs.3.rs-11368506/v1},
url = {https://doi.org/10.21203/rs.3.rs-11368506/v1},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Inflammatory biomarker candidates in dementia with Lewy bodies: diagnostic classification, clinical associations, and survival
AU - Ariana Pritha
AU - Peter Swann
AU - Maura Malpetti
AU - Anna McKeever
AU - Elijah Mak
AU - George Savulich
AU - Ajenthan Surendranathan
AU - Owen Swann
AU - Amanda Heslegrave
AU - Henrik Zetterberg
AU - James B. Rowe
AU - Leonidas Chouliaras
AU - John T. O'Brien
PY - 2026
DA - 2026/11/01
PB - Research Square
DO - 10.21203/rs.3.rs-11368506/v1
UR - https://doi.org/10.21203/rs.3.rs-11368506/v1
AB - 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.
SN - 2693-5015
ER -