Studies suggest a role of the innate immune system, including the activity of neutrophils, in neurodegeneration related to Alzheimer’s disease (AD), but prospective cognitive data remain lacking in humans. We aimed to investigate the predictive relationship between neutrophil-associated inflammatory proteins in peripheral blood and changes in memory and executive function over 1 year in patients with AD. Participants with AD were identified from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Neutrophil gelatinase-associated lipocalin (NGAL), myeloperoxidase (MPO), interleukin-8 (IL-8), macrophage inflammatory protein-1 beta (MIP-1β), and tumor necrosis factor (TNF) were assayed by luminex immunofluorescence multiplex assay at baseline. Confirmatory factor analysis was used to test an underlying neutrophil associated plasma inflammatory factor. Composite z-scores for memory and executive function were generated from multiple tests at baseline and at 1 year. A multiple linear regression model was used to investigate the association of the baseline inflammatory factor with changes in memory and executive function over 1 year. Among AD patients (n = 109, age = 74.8 ± 8.1, 42% women, Mini Mental State Examination [MMSE] = 23.6 ± 1.9), the neutrophil-related inflammatory proteins NGAL (λ = 0.595, p < .001), MPO (λ = 0.575, p < .001), IL-8 (λ = 0.525, p < .001), MIP-1β (λ = 0.411, p = .008), and TNF (λ = 0.475, p < .001) were found to inform an underlying factor. Over 1 year, this inflammatory factor predicted a decline in executive function (β = − 0.152, p = 0.015) but not memory (β = 0.030, p = 0.577) in models controlling for demographics, brain atrophy, white matter hyperintensities, the ApoE ε4 allele, concomitant medications, and baseline cognitive performance. An inflammatory factor constructed from five neutrophil-related markers in peripheral blood predicted a decline in executive function over 1 year in people with mild AD.

中文翻译：

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周围性中性粒细胞相关的炎症因子预测轻度阿尔茨海默氏病的执行功能下降

研究表明，先天免疫系统（包括嗜中性粒细胞的活性）在与阿尔茨海默氏病（AD）有关的神经退行性变中的作用，但人类仍缺乏前瞻性认知数据。我们旨在调查AD患者1年以上外周血中性粒细胞相关炎症蛋白与记忆和执行功能变化之间的预测关系。从阿尔茨海默氏病神经影像学计划（ADNI）中识别出患有AD的参与者。中性粒细胞明胶酶相关的脂蛋白（NGAL），髓过氧化物酶（MPO），白细胞介素8（IL-8），巨噬细胞炎性蛋白1β（MIP-1β）和肿瘤坏死因子（TNF）分别通过luminex免疫荧光多重分析基线。验证性因子分析用于测试潜在的中性粒细胞相关血浆炎症因子。在基线和1年时通过多次测试生成了用于记忆和执行功能的复合z评分。使用多元线性回归模型研究基线炎症因子与1年以上记忆力和执行功能变化的关系。在AD患者中（n = 109，年龄= 74.8±8.1，42％的女性，迷你精神状态检查[MMSE] = 23.6±1.9），中性粒细胞相关的炎症蛋白NGAL（λ= 0.595，p <.001），MPO （λ= 0.575，p <.001），IL-8（λ= 0.525，p <.001），MIP-1β（λ= 0.411，p = .008）和TNF（λ= 0.475，p <.001） ）被发现可告知潜在因素。在1年多的时间里，该炎症因子预测执行功能会下降（β= − 0.152，p = 0。015），但在控制人口统计学，脑萎缩，白质高信号，ApoEε4等位基因，伴随用药和基线认知表现的模型中没有记忆（β= 0.030，p = 0.577）。由外周血中五个与中性粒细胞相关的标志物构成的炎症因子预测轻度AD患者的执行功能将在1年内下降。