The association between Alzheimer-associated neuronal thread protein (AD7c-NTP) and plasma inflammatory cytokine levels in individuals with cognitive impairment and demographically-matched controls

Abstract

Background

Alzheimer-associated neuronal thread protein (AD7c-NTP) has emerged as a potential diagnostic biomarker for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Growing research indicates neuroinflammatory mechanisms contribute to AD pathogenesis.

Objective

To investigate the relationship between AD7c-NTP level and inflammatory biomarkers.

Methods

This cross-sectional study enrolled 112 participants comprising 72 cognitively impaired individuals (CI group) and 40 demographically matched controls with cognitively normal (CN group). Comprehensive physical evaluations and standardized neuropsychological assessments were administered. Urinary AD7c-NTP concentrations were quantified through enzyme-linked immunosorbent assay (ELISA), while plasma levels of twelve inflammatory markers—IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, TNF-α, IFN-α, and IFN-γ—were analyzed via flow cytometry-based immunofluorescence techniques.

Results

Concentrations of IL-2, IFN-α, and IFN-γ showed marked elevation in CI patients relative to CN controls (p = 0.005, 0.008, and 0.010, respectively). Strong positive associations emerged between AD7c-NTP concentrations and both IL-2 (r = 0.492, p < 0.001) and IFN-α (r = 0.492, p < 0.001). The four-marker panel (AD7c-NTP combined with IL-2, IFN-α, and IFN-γ) achieved optimal diagnostic accuracy for cognitive impairment, yielding an AUC value of 0.9774 with 94% sensitivity and 75% specificity.

Conclusions

Integrating IL-2, IFN-α, and IFN-γ measurements with AD7c-NTP detection could constitute a superior diagnostic framework for early-stage cognitive decline. The observed correlations between AD7c-NTP and these cytokine profiles may indicate previously unrecognized metabolic pathways relevant to AD pathology.