Inflammatory changes in early dementia with Lewy bodies

ObjectiveTo examine if immune cell changes are present in early stages of Dementia with Lewy Bodies (DLB).BackgroundEvidence for inflammation in synucleinopathies has been building. An extensive number of studies have documented inflammatory changes in Parkinson’s disease (PD), but much less is know...

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Main Authors: Talene A. Yacoubian, Hongwei Qin, Amy Amara, Natividad Stover, Lauren Ruffrage, Yue Zhang, Richard Kennedy, David Geldmacher, Adam Gerstenecker, David G. Standaert, Etty N. Benveniste
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2025.1640614/full
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author Talene A. Yacoubian
Hongwei Qin
Amy Amara
Natividad Stover
Lauren Ruffrage
Yue Zhang
Richard Kennedy
David Geldmacher
Adam Gerstenecker
David G. Standaert
Etty N. Benveniste
author_facet Talene A. Yacoubian
Hongwei Qin
Amy Amara
Natividad Stover
Lauren Ruffrage
Yue Zhang
Richard Kennedy
David Geldmacher
Adam Gerstenecker
David G. Standaert
Etty N. Benveniste
author_sort Talene A. Yacoubian
collection DOAJ
description ObjectiveTo examine if immune cell changes are present in early stages of Dementia with Lewy Bodies (DLB).BackgroundEvidence for inflammation in synucleinopathies has been building. An extensive number of studies have documented inflammatory changes in Parkinson’s disease (PD), but much less is known about DLB. Post-mortem DLB brains show T-cell infiltration, and flow cytometry and cytokine/chemokine measures in DLB subjects have suggested the presence of inflammatory responses in DLB. However, there is limited understanding if immune cell changes are present at the earliest stages of DLB.MethodsWe recruited a small, exploratory cohort of nine subjects with Mild Cognitive Impairment—Lewy Bodies (MCI-LB) as part of the broader Alabama Udall cohort study, which is focused on the role of inflammation in early PD. The MCI-LB cohort was compared to subjects with de novo PD (n = 64) and healthy controls (n = 70) from the larger Alabama Udall cohort. Subjects underwent clinical assessments, including Movement Disorder Society-United Parkinson’s Disease rating scale (MDS-UPDRS), and comprehensive cognitive assessment. Blood was obtained for flow cytometry and cytokine/chemokine analyses.ResultsDemographics and medical history were comparable between groups. Significant differences in University of Pennsylvania Smell Identification Test, Schwab and England Activities of Daily Living, and MDS-UPDRS scores were observed between the groups. MCI-LB subjects had poorer cognitive composite scores compared to PD participants. MCI-LB subjects demonstrated a robust 60% reduction in mature neutrophils compared to healthy controls.ConclusionOur data show changes in innate immune cells in MCI-LB compared to healthy controls in this small exploratory study. A larger cohort study is needed to validate these findings.
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spelling doaj-art-613acb9ca7794426b6f30f6ee1b7de192025-08-26T04:13:11ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-08-011610.3389/fneur.2025.16406141640614Inflammatory changes in early dementia with Lewy bodiesTalene A. Yacoubian0Hongwei Qin1Amy Amara2Natividad Stover3Lauren Ruffrage4Yue Zhang5Richard Kennedy6David Geldmacher7Adam Gerstenecker8David G. Standaert9Etty N. Benveniste10Department of Neurology, Birmingham, AL, United StatesDepartment of Cell, Developmental, and Integrative Biology, Birmingham, AL, United StatesDepartment of Neurology, Birmingham, AL, United StatesDepartment of Neurology, Birmingham, AL, United StatesDepartment of Neurology, Birmingham, AL, United StatesDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Neurology, Birmingham, AL, United StatesDepartment of Neurology, Birmingham, AL, United StatesDepartment of Neurology, Birmingham, AL, United StatesDepartment of Cell, Developmental, and Integrative Biology, Birmingham, AL, United StatesObjectiveTo examine if immune cell changes are present in early stages of Dementia with Lewy Bodies (DLB).BackgroundEvidence for inflammation in synucleinopathies has been building. An extensive number of studies have documented inflammatory changes in Parkinson’s disease (PD), but much less is known about DLB. Post-mortem DLB brains show T-cell infiltration, and flow cytometry and cytokine/chemokine measures in DLB subjects have suggested the presence of inflammatory responses in DLB. However, there is limited understanding if immune cell changes are present at the earliest stages of DLB.MethodsWe recruited a small, exploratory cohort of nine subjects with Mild Cognitive Impairment—Lewy Bodies (MCI-LB) as part of the broader Alabama Udall cohort study, which is focused on the role of inflammation in early PD. The MCI-LB cohort was compared to subjects with de novo PD (n = 64) and healthy controls (n = 70) from the larger Alabama Udall cohort. Subjects underwent clinical assessments, including Movement Disorder Society-United Parkinson’s Disease rating scale (MDS-UPDRS), and comprehensive cognitive assessment. Blood was obtained for flow cytometry and cytokine/chemokine analyses.ResultsDemographics and medical history were comparable between groups. Significant differences in University of Pennsylvania Smell Identification Test, Schwab and England Activities of Daily Living, and MDS-UPDRS scores were observed between the groups. MCI-LB subjects had poorer cognitive composite scores compared to PD participants. MCI-LB subjects demonstrated a robust 60% reduction in mature neutrophils compared to healthy controls.ConclusionOur data show changes in innate immune cells in MCI-LB compared to healthy controls in this small exploratory study. A larger cohort study is needed to validate these findings.https://www.frontiersin.org/articles/10.3389/fneur.2025.1640614/fullParkinson’s diseasedementia with Lewy bodiesinflammationcognitionneutrophils
spellingShingle Talene A. Yacoubian
Hongwei Qin
Amy Amara
Natividad Stover
Lauren Ruffrage
Yue Zhang
Richard Kennedy
David Geldmacher
Adam Gerstenecker
David G. Standaert
Etty N. Benveniste
Inflammatory changes in early dementia with Lewy bodies
Frontiers in Neurology
Parkinson’s disease
dementia with Lewy bodies
inflammation
cognition
neutrophils
title Inflammatory changes in early dementia with Lewy bodies
title_full Inflammatory changes in early dementia with Lewy bodies
title_fullStr Inflammatory changes in early dementia with Lewy bodies
title_full_unstemmed Inflammatory changes in early dementia with Lewy bodies
title_short Inflammatory changes in early dementia with Lewy bodies
title_sort inflammatory changes in early dementia with lewy bodies
topic Parkinson’s disease
dementia with Lewy bodies
inflammation
cognition
neutrophils
url https://www.frontiersin.org/articles/10.3389/fneur.2025.1640614/full
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