Johansson Per, Almqvist Erik G, Wallin Anders, Johansson Jan-Ove, Andreasson Ulf, Blennow Kaj, Zetterberg Henrik, Svensson Johan
Department of Neuropsychiatry, Skaraborg Central Hospital, Falköping, Sweden.
Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
PLoS One. 2017 May 2;12(5):e0176760. doi: 10.1371/journal.pone.0176760. eCollection 2017.
The role of inflammation in Alzheimer's disease (AD) and other cognitive disorders is unclear. In a well-defined mono-center population, we measured cytokines and chemokines in paired serum and cerebrospinal fluid (CSF) samples.
Consecutive patients with AD (n = 30), stable mild cognitive impairment (SMCI, n = 11), other dementias (n = 11), and healthy controls (n = 18) were included. None of the subjects was treated with glucocorticoids, cholinesterase inhibitors, or non-steroidal anti-inflammatory drugs. Serum and CSF concentrations of interleukin-6 (IL-6), IL-8, IL-12/23 p40, IL-15, IL-16, vascular endothelial growth factor-A (VEGF-A), and three chemokines were measured using a multiplex panel.
After correction for multiple comparisons, only CSF IL-12/23 p40 concentration differed significantly between the total patient group (n = 52) and controls (n = 18; p = 0.002). Further analyses showed that CSF IL-12/23 p40 concentration was decreased in all patient subgroups (AD, other dementias, and SMCI) compared to healthy controls (p < 0.01, p < 0.05, and p < 0.05, respectively). In the total study population (n = 70), CSF IL-12/23 p40 concentrations correlated positively with CSF concentrations of β-amyloid1-42 (Aβ1-42) and phosphorylated tau protein (P-tau) whereas in AD patients (n = 30), CSF IL-12/23 p40 only correlated positively with CSF P-Tau (r = 0.46, p = 0.01).
Most cytokines and chemokines were similar in patients and controls, but CSF IL-12/23 subunit p40 concentration was decreased in patients with cognitive impairment, and correlated with markers of AD disease status. Further studies are needed to evaluate the role of CSF IL-12/23 p40 in other dementias and SMCI.
炎症在阿尔茨海默病（AD）及其他认知障碍中的作用尚不清楚。在一个明确界定的单中心人群中，我们检测了配对的血清和脑脊液（CSF）样本中的细胞因子和趋化因子。
纳入连续的AD患者（n = 30）、稳定的轻度认知障碍（SMCI，n = 11）、其他痴呆患者（n = 11）以及健康对照者（n = 18）。所有受试者均未接受糖皮质激素、胆碱酯酶抑制剂或非甾体抗炎药治疗。使用多重检测板检测血清和脑脊液中白细胞介素-6（IL-6）、IL-8、IL-12/23 p40、IL-15、IL-16、血管内皮生长因子-A（VEGF-A）以及三种趋化因子的浓度。
在进行多重比较校正后，仅患者总体组（n = 52）与对照组（n = 18；p = 0.002）之间的脑脊液IL-12/23 p40浓度存在显著差异。进一步分析表明，与健康对照相比，所有患者亚组（AD、其他痴呆和SMCI）的脑脊液IL-12/23 p40浓度均降低（分别为p < 0.01、p < 0.05和p < 0.05）。在整个研究人群（n = 70）中，脑脊液IL-12/23 p40浓度与脑脊液β-淀粉样蛋白1-42（Aβ1-42）和磷酸化tau蛋白（P-tau）浓度呈正相关，而在AD患者（n = 30）中，脑脊液IL-12/23 p40仅与脑脊液P-Tau呈正相关（r = 0.46，p = 0.01）。
患者和对照者的大多数细胞因子和趋化因子相似，但认知障碍患者的脑脊液IL-12/23亚基p40浓度降低，且与AD疾病状态标志物相关。需要进一步研究以评估脑脊液IL-12/23 p40在其他痴呆和SMCI中的作用。
