Xerogel-Engineered Graphitic Carbon Nitride Interfaces Enable Aptamer-Based Detection of Salivary Lactoferrin for Noninvasive Diagnosis of Alzheimer’s Disease

Alzheimer’s disease (AD), the primary cause of dementia, is a progressive neurodegenerative disorder that requires early diagnosis using noninvasive biosensing strategies. Salivary lactoferrin has consequently emerged as a compelling early-stage AD biomarker, as its dysregulated expression reflects underlying neuroinflammatory mechanisms associated with disease initiation and progression. Accordingly, we report an innovative aptamer-based electrochemical aptasensor for noninvasive and accurate biosensing of salivary lactoferrin (Lf). The design approach involves fabricating gold screen-printed electrodes (gSPEs) with in situ prepared porous graphitic carbon nitride (g-C3N4) xerogel using coprecipitation with the amino acid l-cysteine (l-Cys), followed by surface immobilization of the Lf aptamer and subsequent blocking with 6-mercapto-1-hexanol (MCH) via drop-casting. Structural and electrochemical characterizations indicate successful xerogel synthesis, where l-Cys acts as an interlayer-bridging agent, achieving high specificity and superior performance within a broad detection range of 0.5–500 μg mL–1 based on the differential pulse voltammetry (DPV) technique. The aptasensor exhibits a significantly high sensitivity of 89.22 μA (log10 μg mL–1)−1 cm–2 and a low limit of detection (LOD) of 0.34 μg mL–1 in the artificial saliva samples. Furthermore, our fabricated sensor shows good reproducibility and repeatability with %RSD values well below 5%, thereby strengthening the utility of our novel biosensor design for applications in the timely detection of AD biomarker in body fluids, both within clinical settings as well as in point-of-care (POC) diagnostics.