Yacoubian Talene A, Qin Hongwei, Amara Amy, Stover Natividad, Ruffrage Lauren, Zhang Yue, Kennedy Richard, Geldmacher David, Gerstenecker Adam, Standaert David G, Benveniste Etty N
Department of Neurology, Birmingham, AL, United States.
Department of Cell, Developmental, and Integrative Biology, Birmingham, AL, United States.
Front Neurol. 2025 Aug 26;16:1640614. doi: 10.3389/fneur.2025.1640614. eCollection 2025.
To examine if immune cell changes are present in early stages of Dementia with Lewy Bodies (DLB).
Evidence 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.
We 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 PD ( = 64) and healthy controls ( = 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.
Demographics 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.
Our 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.
研究路易体痴呆(DLB)早期是否存在免疫细胞变化。
关于突触核蛋白病中炎症的证据不断积累。大量研究记录了帕金森病(PD)中的炎症变化,但对DLB的了解要少得多。DLB患者的尸检大脑显示有T细胞浸润,DLB患者的流式细胞术和细胞因子/趋化因子检测表明存在炎症反应。然而,对于DLB最早阶段是否存在免疫细胞变化的了解有限。
作为更广泛的阿拉巴马尤德尔队列研究的一部分,我们招募了一个由9名轻度认知障碍路易体(MCI-LB)患者组成的小型探索性队列,该研究主要关注炎症在早期PD中的作用。将MCI-LB队列与来自更大的阿拉巴马尤德尔队列的PD患者(n = 64)和健康对照者(n = 70)进行比较。受试者接受了包括运动障碍协会统一帕金森病评定量表(MDS-UPDRS)在内的临床评估和全面的认知评估。采集血液进行流式细胞术和细胞因子/趋化因子分析。
各组之间的人口统计学和病史具有可比性。在宾夕法尼亚大学嗅觉识别测试、施瓦布和英格兰日常生活活动量表以及MDS-UPDRS评分方面,各组之间存在显著差异。与PD参与者相比,MCI-LB患者的认知综合评分较差。与健康对照者相比,MCI-LB患者的成熟中性粒细胞减少了60%。
在这项小型探索性研究中,我们的数据显示MCI-LB患者与健康对照者相比,固有免疫细胞发生了变化。需要更大规模的队列研究来验证这些发现。