Multiplex analyte assays to characterize different dementias: brain inflammatory cytokines in poststroke and other dementias.
Multiplex analyte assays to characterize different dementias: brain inflammatory cytokines in poststroke and other dementias.
复制标题
多重分析物测定以表征不同的痴呆症：脑抑制后和其他痴呆症中的脑炎症细胞因子。
DOI：
10.1016/j.neurobiolaging.2015.10.021
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发表时间：
2016-02
影响因子：
4.2
通讯作者：
Kalaria RN
中科院分区：
文献类型：
--
作者：
Chen A;Oakley AE;Monteiro M;Tuomela K;Allan LM;Mukaetova-Ladinska EB;O'Brien JT;Kalaria RN
炎症潜能和认知功能都会随着年龄的增长而下降。炎性生物标志物与认知功能下降之间的联系尚不清楚。据报道，在痴呆症患者的脑脊液和血清中，炎性细胞因子增加、减少或没有变化。我们评估了112名被诊断为中风后痴呆(PSD)、血管性痴呆、混合性痴呆和阿尔茨海默病(AD)的受试者的死后大脑，并将其与中风后非痴呆(PSND)受试者和年龄匹配的对照组进行了比较。我们分析了5个大脑区域，包括来自额叶和颞叶的灰质和白质，用于一组细胞因子和/或趋化因子分析物的多重阵列分析。在37种分析物中，14种低于或接近检测限，7种接近最低检测水平，16种细胞因子在测定的线性范围内。我们观察到C反应蛋白(CRP)和血清淀粉样蛋白A在高端(1-150 ng/mg蛋白)的浓度变化很大，而在低端(1-10 pg/mg蛋白)有几种白介素类(IL、干扰素-γ和肿瘤坏死因子)。也有区域差异；最值得注意的是额叶白质中某些细胞因子(例如，CRP和血管生成面板)的高浓度。总体而言，我们发现在所有痴呆组中，几种细胞因子的浓度降低，包括IL-1β(p=0.000)，IL-6(p=0.000)，IL-7(p=0.000)，IL-8(p=0.000)，IL-16(p=0.001)，干扰素诱导蛋白-10(p=0.044)，血清淀粉样蛋白A(p=0.011)，以及与非痴呆对照组相比，IL-1α(p=0.084)的趋势。各地区痴呆组IL-6和IL-8水平均显著低于非痴呆组。特别是，与PSND受试者相比，PSD患者的IL-6和IL-8水平显著降低。由于这两组卒中患者的血管病变程度相当，PSD中IL-6和IL-8的低水平产生再次证实了免疫衰老可能参与了痴呆的发病机制。相反，在痴呆症和非痴呆症受试者之间，或者在PSD和PSND之间，CRP没有改变。我们的研究不仅为追踪死后脑组织中细胞因子的可行性提供了证据，还提示了痴呆(包括阿尔茨海默病)的不同受损的炎症机制。在所有痴呆患者中，炎症反应减弱，可能反映了免疫衰老和脑萎缩。增强抗炎细胞因子和增强大脑免疫系统的策略可能有助于预防认知功能障碍，特别是中风后。
Both the inflammatory potential and cognitive function decline during aging. The association between the repertoire of inflammatory biomarkers and cognitive decline is unclear. Inflammatory cytokines have been reported to be increased, decreased, or unchanged in the cerebrospinal fluid and sera of subjects with dementia. We assessed 112 postmortem brains from subjects diagnosed with poststroke dementia (PSD), vascular dementia, mixed dementia, and Alzheimer's disease (AD), comparing those to poststroke nondemented (PSND) subjects and age-matched controls. We analyzed 5 brain regions including the gray and white matter from the frontal and temporal lobes for a panel of cytokine and/or chemokine analytes using multiplex-array assays. Of the 37 analytes, 14 were under or near the detection limits, 7 were close to the lowest detection level, and 16 cytokines were within the linear range of the assay. We observed widely variable concentrations of C-reactive protein (CRP) and serum amyloid A at the high end (1–150 ng/mg protein), whereas several of the interleukins (IL, interferon-gamma and tumor necrosis factor) at the low end (1–10 pg/mg). There were also regional variations; most notable being high concentrations of some cytokines (e.g., CRP and angiogenesis panel) in the frontal white matter. Overall, we found decreased concentrations of several cytokines, including IL-1 beta (p = 0.000), IL-6 (p = 0.000), IL-7 (p = 0.000), IL-8 (p = 0.000), IL-16 (p = 0.001), interferon-inducible protein–10 (0.044), serum amyloid A (p = 0.011), and a trend in IL-1 alpha (p = 0.084) across all dementia groups compared to nondemented controls. IL-6 and IL-8 were significantly lower in dementia subjects than in nondemented subjects in every region. In particular, lower levels of IL-6 and IL-8 were notable in the PSD compared to PSND subjects. Because these 2 stroke groups had comparable degree of vascular pathology, the lower production of IL-6 and IL-8 in PSD reaffirms a possible specific involvement of immunosenescence in dementia pathogenesis. In contrast, CRP was not altered between dementia and nondementia subjects or between PSD and PSND. Our study provides evidence not only for the feasibility of tracking cytokines in postmortem brain tissue but also suggests differentially impaired inflammatory mechanisms underlying dementia including AD. There was a diminished inflammatory response, possibly reflecting immunosenescence and cerebral atrophy, in all dementias. Strategies to enhance anti-inflammatory cytokines and boost the immune system of the brain may be beneficial for preventing cognitive dysfunction, especially after stroke.