Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville 3000, Australia.
Department of Medicine, The Royal Melbourne Hospital, University of Melbourne, Parkville 3000, Australia.
Int J Mol Sci. 2023 Jul 28;24(15):12116. doi: 10.3390/ijms241512116.
Inflammatory mechanisms are increasingly recognized as important contributors to the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Our objectives were to, firstly, review inflammation investigation methods in LBD (dementia with Lewy bodies and Parkinson's disease dementia) and, secondly, identify alterations in inflammatory signals in LBD compared to people without neurodegenerative disease and other neurodegenerative diseases. A systematic scoping review was performed by searching major electronic databases (MEDLINE, Embase, Web of Science, and PSYCHInfo) to identify relevant human studies. Of the 2509 results screened, 80 studies were included. Thirty-six studies analyzed postmortem brain tissue, and 44 investigated living subjects with cerebrospinal fluid, blood, and/or brain imaging assessments. Largely cross-sectional data were available, although two longitudinal clinical studies investigated prodromal Lewy body disease. Investigations were focused on inflammatory immune cell activity (microglia, astrocytes, and lymphocytes) and inflammatory molecules (cytokines, etc.). Results of the included studies identified innate and adaptive immune system contributions to inflammation associated with Lewy body pathology and clinical disease features. Different signals in early and late-stage disease, with possible late immune senescence and dystrophic glial cell populations, were identified. The strength of these associations is limited by the varying methodologies, small study sizes, and cross-sectional nature of the data. Longitudinal studies investigating associations with clinical and other biomarker outcomes are needed to improve understanding of inflammatory activity over the course of LBD. This could identify markers of disease activity and support therapeutic development.
炎症机制越来越被认为是神经退行性疾病发病机制的重要因素，包括路易体痴呆（LBD）。我们的目标是，首先，回顾 LBD（路易体痴呆和帕金森病痴呆）中的炎症研究方法，其次，确定与无神经退行性疾病和其他神经退行性疾病的人相比，LBD 中炎症信号的变化。通过搜索主要电子数据库（MEDLINE、Embase、Web of Science 和 PSYCHInfo），进行了系统的范围综述，以确定相关的人类研究。在筛选出的 2509 个结果中，有 80 项研究被纳入。36 项研究分析了死后脑组织，44 项研究调查了有脑脊液、血液和/或脑成像评估的活体受试者。虽然有两项纵向临床研究调查了前驱性路易体疾病，但主要是横断面数据。研究集中在炎症免疫细胞活性（小胶质细胞、星形胶质细胞和淋巴细胞）和炎症分子（细胞因子等）上。纳入研究的结果确定了固有和适应性免疫系统对与路易体病理学和临床疾病特征相关的炎症的贡献。在疾病的早期和晚期阶段，可能存在晚期免疫衰老和退行性神经胶质细胞群，发现了不同的信号。这些关联的强度受到不同方法、研究规模小以及数据的横断面性质的限制。需要进行纵向研究，以调查与临床和其他生物标志物结果的关联，从而更好地了解 LBD 过程中的炎症活性。这可以确定疾病活动的标志物，并支持治疗方法的开发。
