Investigating the correlation between neutrophil-to-lymphocyte ratio and blood-based markers in clinically diagnosed Alzheimer’s disease and cognitive impairment

Abstract Background : Neuroinflammation is recognized as a critical factor in the pathogenesis of Alzheimer’s disease (AD). The neutrophil-to-lymphocyte ratio (NLR) serves as a straightforward peripheral indicator of systemic inflammation; however, its association with blood-based biomarkers of AD and cognitive function remains inadequately understood. Methods : A total of 228 participants, comprising 117 cognitively unimpaired individuals and 111 with AD-related cognitive impairment, aged between 46 and 84 years, were enrolled in this study. Each participant underwent comprehensive clinical and neuropsychological assessments, APOE genotyping, and fasting blood sampling. Plasma levels of amyloid-β 42/40 (Aβ42/40), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau181 (p-tau181) were quantified using the Simoa platform. The relationships between NLR, cognitive performance scores, and AD biomarkers were evaluated using Spearman correlation coefficients and multivariate regression models, with adjustments for potential confounding variables. Additionally, mediation analyses were conducted employing bootstrap methods. Results : In comparison to the unimpaired group, individuals with cognitive impairment exhibited increased neutrophil counts, elevated NLR, and higher GFAP, NfL, and p-tau181, alongside a reduced Aβ42/40 ratio. The NLR demonstrated a negative correlation with cognitive scores and a positive correlation with GFAP, NfL, and p-tau181, with the strongest correlation observed for NfL. Multivariate regression analysis indicated that NLR remained independently associated with GFAP, NfL, and p-tau181 after controlling for age, education, and other covariates. Mediation analysis suggested that NLR partially mediated the relationships between GFAP, NfL, and p-tau181 and cognitive performance, but not the relationship with Aβ42/40. Conclusion : Elevated NLR is linked to poorer cognitive function and higher plasma concentrations of GFAP, NfL, and p-tau181, with the most pronounced association observed for NfL. NLR has the potential to serve as a cost-effective peripheral biomarker for AD-related cognitive decline.