Rembach Alan, Watt Andrew D, Wilson William J, Rainey-Smith Stephanie, Ellis Kathryn A, Rowe Christopher C, Villemagne Victor L, Macaulay S Lance, Bush Ashley I, Martins Ralph N, Ames David, Masters Colin L, Doecke James D
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3052, Australia.
CSIRO Computational Informatics/Australian e-Health Research Centre, Royal Brisbane and Women's Hospital, Brisbane, QLD 4029, Australia.
J Neuroimmunol. 2014 Aug 15;273(1-2):65-71. doi: 10.1016/j.jneuroim.2014.05.005. Epub 2014 May 20.
Inflammation is a hallmark of Alzheimer's disease (AD). Whether directly involved in the pathogenesis, or a downstream consequence of neuronal death, the blood neutrophil-lymphocyte ratio (NLR) is reported to be a putative, non-invasive peripheral biomarker for AD. The aim of this study was to re-evaluate the diagnostic utility of longitudinal measures of the NLR. The NLR was stable across all time-points and weakly correlated with neocortical amyloid burden (R=0.21 at baseline, 0.27 at 18 months, 0.20 at 36 months and 0.10 at 54 months). Cross-sectionally, the NLR was significantly elevated in AD participants as compared to HC participants at baseline (p<0.0001), 18 months (p<0.0001), 36 months (p=0.002) and at 54 months (p=0.007), however only prior to adjustment for age, sex and APOEε4 allele status (p>0.05 at all time-points except for 18 months; p<0.0001). Longitudinally, the NLR was not significantly different between HC and AD participants (p>0.05) adjusted for age, sex and APOEε4 allele status. Comparing the NLR between cognitive transition groups over time (transition towards an AD type dementia), there was no significant difference in the NLR levels between those participants, who did not transition and those participants who did transition, or those in the stable AD group after adjusting for age, sex and APOEε4 allele status (p>0.05). Despite inflammation being a hallmark in AD and previous reports showing that the NLR can discriminate HC from AD patients, our results suggest that the sensitivity of the NLR itself is not robust enough for diagnostic utility. We identified significant relationships cross sectionally (p<0.05 at baseline, 18 months and 36 months) between the NLR and neocortical amyloid burden, but this relationship was lost after longitudinal analyses (p>0.5). The NLR also had limited association with cognitive decline, although in our cohort, the number of participants transitioning was relatively small. In conclusion, the NLR may reflect AD-related inflammatory processes in the periphery, but age and sex are dominant covariates which need to be controlled for in population-based screening.
炎症是阿尔茨海默病（AD）的一个标志。无论炎症是直接参与发病机制，还是神经元死亡的下游后果，据报道血液中性粒细胞与淋巴细胞比值（NLR）是一种假定的、非侵入性的AD外周生物标志物。本研究的目的是重新评估NLR纵向测量的诊断效用。NLR在所有时间点都很稳定，并且与新皮质淀粉样蛋白负荷呈弱相关（基线时R = 0.21，18个月时为0.27，36个月时为0.20，54个月时为0.10）。横断面分析显示，与健康对照（HC）参与者相比，AD参与者在基线时（p < 0.0001）、18个月时（p < 0.0001）、36个月时（p = 0.002）和54个月时（p = 0.007）的NLR显著升高，然而，这仅在未对年龄、性别和APOEε4等位基因状态进行校正之前成立（除18个月外，所有时间点p > 0.05；p < 0.0001）。纵向分析表明，在对年龄、性别和APOEε4等位基因状态进行校正后，HC和AD参与者之间的NLR没有显著差异（p > 0.05）。随着时间推移比较认知转变组之间的NLR（向AD型痴呆转变），在对年龄、性别和APOEε4等位基因状态进行校正后，未转变的参与者与转变的参与者之间，或稳定AD组参与者之间的NLR水平没有显著差异（p > 0.05）。尽管炎症是AD的一个标志，且先前的报告表明NLR可以区分HC和AD患者，但我们的数据表明，NLR本身的敏感性不足以用于诊断。我们在横断面分析中发现NLR与新皮质淀粉样蛋白负荷之间存在显著关系（基线、18个月和36个月时p < 0.05），但在纵向分析后这种关系消失了（p > 0.5）。NLR与认知衰退的关联也有限，尽管在我们的队列中，转变的参与者数量相对较少。总之，NLR可能反映了外周与AD相关的炎症过程，但年龄和性别是主要的协变量，在基于人群的筛查中需要对其进行控制。
