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

**Authors:** Alev Lazoglu Ozkaya, Nilifer Gürbüzer, Tolga Mercantepe, Filiz Mercantepe

PMC · DOI: 10.3390/biom15060795 · Biomolecules · 2025-05-30

## TL;DR

This study found that lower levels of NPAS-4 and NPTX-2 in blood may indicate Alzheimer’s disease, suggesting they could help in early diagnosis.

## Contribution

The study identifies NPAS-4 and NPTX-2 as novel serum biomarkers for synaptic dysfunction in Alzheimer’s disease.

## Key findings

- Serum NPAS-4 and NPTX-2 levels were significantly lower in Alzheimer’s patients compared to controls.
- NPAS-4 was identified as an independent risk predictor for Alzheimer’s disease.
- Both biomarkers showed significant diagnostic discrimination power in ROC analysis.

## Abstract

Background: 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. Objective: 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. Methods: 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. Results: Serum NPAS-4 and NPTX-2 levels were significantly lower in Alzheimer’s patients compared to healthy controls (p < 0.001 and p = 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, p < 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. Conclusions: 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.

## Linked entities

- **Genes:** NPAS4 (neuronal PAS domain protein 4) [NCBI Gene 266743], NPTX2 (neuronal pentraxin 2) [NCBI Gene 4885]
- **Diseases:** Alzheimer’s disease (MONDO:0004975)

## Full-text entities

- **Genes:** NPAS4 (neuronal PAS domain protein 4) [NCBI Gene 266743] {aka Le-PAS, NXF, PASD10, bHLHe79}, NPTX2 (neuronal pentraxin 2) [NCBI Gene 4885] {aka NARP, NP-II, NP2}
- **Diseases:** neurodegenerative disorder (MESH:D019636), Synaptic Dysfunction (MESH:C536122), cognitive decline (MESH:D003072), AD (MESH:D000544), neuronal loss (MESH:D009410)
- **Chemicals:** cholesterol (MESH:D002784), lipid (MESH:D008055)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12191051/full.md

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Source: https://tomesphere.com/paper/PMC12191051