背景:血液中中性粒细胞-淋巴细胞比率(NLR)升高与阿尔茨海默病(AD)有关。然而,NLR升高也与许多其他AD的危险因素有关,促使调查NLR是否与AD病理或潜在合并症直接相关。在这里,我们探讨了认知未受损(CU)受试者脑脊液(CSF)中NLR和AD生物标志物之间的关系.适应社会人口统计学,APOE4和常见的合并症,我们在两个队列中调查了这些关联:阿尔茨海默病神经影像学计划(ADNI)和纽约大学的M.J.deLeonCSF资料库.具体来说,我们检查了NLR和淀粉样β42(Aβ42)的横断面测量值之间的关联,总tau(t-tau),和磷酸化的tau181(p-tau),以及纵向获得的这些CSF测量的轨迹。
结果:共有111名ADNI和190名NYU参与者被分类为CU,并具有可用的NLR,CSF,和协变量数据被包括在内。与纽约大学相比,ADNI参与者年龄较大(73.79vs.61.53,p<0.001),男性比例较高(49.5%vs.36.8%,p=0.042),较高的BMI(27.94vs.25.79,p<0.001),高血压病史患病率较高(47.7%vs.16.3%,p<0.001),Aβ阳性的百分比更高(34.2%vs.20.0%,p=0.009)。在ADNI队列中,我们发现NLR和CSFAβ42之间的横截面关联(β=-12.193,p=0.021),但不是t-tau或p-tau.在纽约大学队列中,我们发现NLR和CSFt-tau(β=26.812,p=0.019)和p-tau(β=3.441,p=0.015)之间的横截面关联,但不是Aβ42。仅在纽约大学队列中,与Aβ-受试者或非分层队列相比,分类为Aβ+(n=38)的受试者显示NLR和t-tau(β=100.476,p=0.037)之间更强的关联.在这两个队列中,纳入纵向CSF数据后,在横断面分析中观察到相同的关联.
结论:我们报告了较老的ADNI队列中NLR和Aβ42之间的关联,在年轻的纽约大学队列中,NLR与t-tau和p-tau之间。在调整合并症后,协会仍然存在,表明NLR和AD之间存在直接联系。然而,NLR与特定AD生物标志物之间的关联变化可能是免疫衰老的一部分.
BACKGROUND: An elevated neutrophil-lymphocyte ratio (NLR) in blood has been associated with Alzheimer\'s disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Herein, we explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer\'s Disease Neuroimaging Initiative (ADNI) and the M.J. de Leon CSF repository at NYU. Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-β42 (Aβ42), total tau (t-tau), and phosphorylated tau181 (p-tau), as well as the trajectories of these CSF measures obtained longitudinally.
RESULTS: A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of Aβ-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aβ42 (β = -12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (β = 26.812, p = 0.019) and p-tau (β = 3.441, p = 0.015), but not Aβ42. In the NYU cohort alone, subjects classified as Aβ + (n = 38) displayed a stronger association between the NLR and t-tau (β = 100.476, p = 0.037) compared to Aβ- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data.
CONCLUSIONS: We report associations between the NLR and Aβ42 in the older ADNI cohort, and between the NLR and t-tau and p-tau in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD biomarkers may occur as part of immunosenescence.