Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Memory Assessment and Research Centre, Southern Health NHS Foundation Trust, Southampton, UK.
J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1219-1226. doi: 10.1136/jnnp-2020-323603. Epub 2020 Sep 23.
Inflammation plays a key role in the aetiology and progression of Alzheimer's disease (AD). However, the immunophenotype of the second most common neurodegenerative cause of dementia, dementia with Lewy bodies (DLB), remains unclear. To date there have been no studies examining peripheral inflammation in DLB using multiplex immunoassay and flow cytometry concomitantly. We hypothesised that, using blood biomarkers, DLB would show an increased proinflammatory profile compared with controls, and that there would be a distinct profile compared with AD.
93 participants (31 with DLB, 31 with AD and 31 healthy older controls) completed a single study visit for neuropsychiatric testing and phlebotomy. Peripheral blood mononuclear cells were quantified for T and B cell subsets using flow cytometry, and serum cytokine concentrations were measured using multiplex immunoassay.
We detected reduced relative numbers of helper T cells and reduced activation of B cells in DLB compared with AD. Additionally, interleukin (IL)-1β was detected more frequently in DLB and the serum concentration of IL-6 was increased compared with controls.
Peripheral inflammation is altered in DLB compared with AD, with T cell subset analysis supporting a possible shift towards senescence of the adaptive immune system in DLB. Furthermore, there is a proinflammatory signature of serum cytokines in DLB. Identification of this unique peripheral immunophenotype in DLB could guide development of an immune-based biomarker and direct future work exploring potential immune modulation as a novel treatment.
炎症在阿尔茨海默病(AD)的发病机制和进展中起着关键作用。然而,第二常见的神经退行性痴呆病因——路易体痴呆(DLB)的免疫表型仍不清楚。迄今为止,尚无研究使用多重免疫分析和流式细胞术同时检查 DLB 的外周炎症。我们假设,使用血液生物标志物,与对照组相比,DLB 会显示出更高的促炎特征,并且与 AD 相比会有明显的特征。
93 名参与者(31 名 DLB,31 名 AD 和 31 名健康老年人对照组)完成了一次神经精神病学测试和采血的单一研究访问。使用流式细胞术对 T 和 B 细胞亚群进行定量,使用多重免疫分析测量血清细胞因子浓度。
与 AD 相比,我们在 DLB 中检测到辅助性 T 细胞数量减少和 B 细胞激活减少。此外,与对照组相比,在 DLB 中更频繁地检测到白细胞介素(IL)-1β,并且 IL-6 的血清浓度增加。
与 AD 相比,DLB 外周炎症发生改变,T 细胞亚群分析支持适应性免疫系统衰老可能向 DLB 转移。此外,DLB 中存在血清细胞因子的促炎特征。在 DLB 中识别这种独特的外周免疫表型可以指导免疫为基础的生物标志物的开发,并指导未来探索潜在免疫调节作为一种新的治疗方法的工作。