Serum Npas-4 and Nptx-2 Levels in Alzheimer’s Disease: Potential Biomarkers of Synaptic Dysfunction in a Cross-Sectional Study

<b>Background:</b> Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, synaptic dysfunction, and neuronal loss. Identifying reliable biomarkers for early diagnosis and disease monitoring remains a critical need. <b>Objective:</b> This study aimed to investigate the serum levels of NPAS-4 (Neuronal PAS Domain Protein 4) and NPTX-2 (Neuronal Pentraxin 2) in patients with Alzheimer's disease, exploring their potential roles in disease pathophysiology and their relationship with lipid parameters. <b>Methods:</b> This was a cross-sectional study that included 63 patients diagnosed with Alzheimer's disease and 56 age- and sex-matched healthy controls. Venous blood samples were collected from all participants. NPAS-4 and NPTX-2 levels were measured using the ELISA method, while lipid parameters were analyzed via spectrophotometric techniques. Cognitive assessment was performed using the Standardized Mini-Mental Test (SMMT). Comparative analyses between groups, correlation studies, logistic regression, and ROC analyses were conducted. <b>Results:</b> Serum NPAS-4 and NPTX-2 levels were significantly lower in Alzheimer's patients compared to healthy controls (<i>p</i> < 0.001 and <i>p</i> = 0.001, respectively). Additionally, total cholesterol and LDL levels were lower in the patient group. Logistic regression analysis identified NPAS-4 as an independent risk predictor for Alzheimer's disease (OR = 0.313, <i>p</i> < 0.001). ROC analyses demonstrated that both biomarkers had significant diagnostic discrimination power. However, no significant correlation was found between NPAS-4 and NPTX-2 levels and SMMT scores or lipid parameters. <b>Conclusions:</b> The decreased levels of NPAS-4 and NPTX-2 in Alzheimer's patients may reflect biochemical manifestations of impaired synaptic plasticity. These findings suggest that NPAS-4 and NPTX-2 may serve as potential early biomarkers in the diagnosis and monitoring of Alzheimer's disease.