Electrochemical Detection of miR-29a and miR-34a Using AuNPs Immobilized by a Silsesquioxane Polyelectrolyte: Potential Early Alzheimer’s Disease Biomarkers Detection

Alzheimer’s Disease (AD) is the leading cause of dementia worldwide, and early diagnosis is crucial to minimize neurological damage and loss of quality of life. Here, we report an electrochemical biosensor for detecting miRNAs 29a and 34a, potential non-invasive biomarkers associated with AD. The biosensor consisted of a glassy carbon electrode (GCE) modified with a novel nanohybrid of gold nanoparticles stabilized by 3-n-propyl(4-dimethylaminopyridinium) silsesquioxane chloride (AuNPs–Si4DMAP+Cl−). Thiolated anti-miRNA probes were immobilized separately on the GCE/AuNPs-Si4DMAP+Cl−, followed by BSA blocking. Target miRNAs were detected via hybridization with complementary probes using electrochemical impedance spectroscopy. The nanohybrid, characterized by spectroscopic and morphological techniques, significantly enhanced the electrochemical response and was effective detecting both miRNAs, showing suspension stability over 600 days. LOD and LOQ were 1.79 pM and 5.87 pM for miRNA-29a, and 2.21 pM and 11.01 pM for miRNA-34a. These results highlight the platform’s potential for electrochemical detection of these miRNAs in blood, supporting earlier detection of AD and other neurodegenerative diseases.