Complement component 3 levels in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder.
Complement component 3 levels in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder.
复制标题
DOI：
10.1016/j.bionps.2019.100007
复制
发表时间：
2019-12-01
影响因子：
--
通讯作者：
Pomara, Nunzio
中科院分区：
文献类型：
--
作者：
Pillai, Anilkumar;Bruno, Davide;Pomara, Nunzio
晚期重度抑郁症（LLMD）是轻度认知障碍和痴呆（包括阿尔茨海默病（AD）和血管性痴呆）发展的危险因素。特别是免疫失调和先天免疫反应的改变，在LLMD和AD的病理生理学中都有牵连。补体系统是先天免疫机制的重要组成部分，在突触可塑性和认知功能中起着重要作用。然而，它在LLMD中的作用仍然未知。在本研究中，我们检测了老年抑郁症受试者脑脊液（CSF）中补体成分3 （C3，所有补体激活途径的交汇点）的水平，并与健康对照组进行了比较；以及CSF C3水平与淀粉样蛋白- β （Abeta42和Abeta40）、总tau （T-tau）和磷酸化tau （P-tau）蛋白和认知评分的关系。从50名认知完整的志愿者（重度抑郁症组，N = 30；对照组，N = 20）中提取脑脊液，用ELISA法分析C3水平。重度抑郁组的C3水平略低于对照组。我们没有发现C3与反映斑块病理的AD生物标志物Abeta42、与tau病理相关的P-tau或神经变性生物标志物T-tau有任何显著关联。C3与CSF Abeta40呈正相关，这可能反映了Abeta在脑血管壁的沉积。在控制教育程度的条件下，我们观察到C3水平与Buschke选择性提醒测试（BSRT）中抑郁症受试者记忆表现的总回忆呈负相关。LLMD受试者C3状态的初步证据可能对我们理解重度抑郁症的病理生理学，特别是晚年抑郁症的病理生理学有启示。
Late-life major depression (LLMD) is a risk factor for the development of mild cognitive impairment and dementia, including Alzheimer's disease (AD) and vascular dementia. Immune dysregulation and changes in innate immune responses in particular, have been implicated in the pathophysiology of both LLMD and AD. Complement system, a key component of the innate immune mechanism, is known to play an important role in synaptic plasticity and cognitive functions. However, its role in LLMD remains unknown. In the present study, we examined the levels of complement component 3 (C3, the convergence point of all complement activation pathways) in the cerebrospinal fluid (CSF) of elderly depressed subjects compared to healthy controls; as well as the relationship of CSF C3 levels with amyloid-beta (Abeta42 and Abeta40), total tau (T-tau) and phosphorylated tau (P-tau) proteins and cognition scores. CSF was obtained from 50 cognitively intact volunteers (major depression group, N = 30; comparison group, N = 20) and analyzed for levels of C3 by ELISA. C3 levels were marginally lower in the major depression group relative to the comparison group. We did not find any significant association of C3 with the AD biomarkers Abeta42 reflecting plaque pathology, P-tau related to tau pathology or the neurodegeneration biomarker T-tau. In contrast, C3 was positively correlated with CSF Abeta40, which may reflect Abeta deposition in cerebral vessel walls. We observed a negative correlation between C3 levels and Total Recall on the Buschke Selective Reminding Test (BSRT) for memory performance in the depressed subjects when controlling for education. This initial evidence on C3 status in LLMD subjects may have implications for our understanding of the pathophysiology of major depression especially in late life.