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Neutrophil activation in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis of protein markers in blood and cerebrospinal fluid.
Ageing Research Reviews ( IF 12.5 ) Pub Date : 2020-07-23 , DOI: 10.1016/j.arr.2020.101130
Che-Yuan Wu 1 , Kritleen K Bawa 1 , Michael Ouk 1 , Nathan Leung 2 , Di Yu 1 , Krista L Lanctôt 3 , Nathan Herrmann 4 , Maureen Pakosh 5 , Walter Swardfager 6
Affiliation  

Inflammation is involved in the pathophysiology of Alzheimer’s disease (AD), with multiple inflammatory processes implicated in its risk and progression. This review included original peer-reviewed studies measuring the cerebrospinal fluid or peripheral blood concentrations of protein markers specifically related to neutrophil activity in healthy controls (HC) and in patients with AD or mild cognitive impairment (MCI). A total of 35 studies (NHC = 3095, NAD = 2596, NMCI = 1203) were included. Random-effects meta-analyses were used to estimate between-groups standardized mean differences (SMD) and 95 % confidence intervals. In blood, concentrations of myeloperoxidase (MPO; NAD/NHC = 271/209, SMD = 0.41 [0.20, 0.62]; I2 = 15.7 %) and neutrophil gelatinase associated lipocalin (NGAL; NAD/NHC = 273/185, SMD = 0.30 [0.11, 0.49]; I2 < 0.005 %) were significantly higher in AD relative to HC. Peripheral blood concentrations of NGAL were also higher in MCI compared to HC (NMCI/NHC = 489/145, SMD = 0.39 [0.11, 0.67]; I2 = 38.6 %). None of the protein markers exhibited a significant difference between HC, MCI, or AD groups in the cerebrospinal fluid. The evidence suggests that peripheral neutrophil activation, as indicated by blood concentrations of NGAL and MPO, may be a pathological feature of cognitive impairment due to AD, evident at stages of MCI and AD dementia.



中文翻译:

阿尔茨海默氏病和轻度认知障碍中的中性粒细胞活化:血液和脑脊液中蛋白质标记物的系统评价和荟萃分析。

炎症与阿尔茨海默氏病(AD)的病理生理有关,涉及其危险性和进展的多种炎症过程。该评价包括同行评审的原始研究,这些研究测量了健康对照(HC)和AD或轻度认知障碍(MCI)患者中脑脊液或外周血中与中性粒细胞活性特别相关的蛋白质标志物的浓度。总共进行了35个研究(N HC = 3095,N AD = 2596,N MCI = 1203)。随机效应荟萃分析用于估计组之间的标准化均值差(SMD)和95%置信区间。血液中的髓过氧化物酶(MPO; N AD / N HC= 271/209,SMD = 0.41 [0.20,0.62];I 2 = 15.7%)和中性粒细胞明胶酶相关脂钙蛋白(NGAL; N AD / N HC = 273 / 185,SMD = 0.30 [0.11,0.49]; I 2 <0.005%)相对于HC在AD中显着升高。与HC相比,MCI中NGAL的外周血浓度也更高(N MCI / N HC = 489 / 145,SMD = 0.39 [0.11,0.67]; I 2= 38.6%)。脑脊液中的HC,MCI或AD组之间没有蛋白标记物表现出显着差异。有证据表明,外周血中性粒细胞活化(如NGAL和MPO的血药浓度所表明)可能是AD引起的认知障碍的病理特征,在MCI和AD痴呆症的阶段很明显。

更新日期:2020-07-23
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