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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\u2013Si4DMAP+Cl\u2212). Thiolated anti-miRNA probes were immobilized separately on the GCE\/AuNPs-Si4DMAP+Cl\u2212, 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\u2019s potential for electrochemical detection of these miRNAs in blood, supporting earlier detection of AD and other neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/s26072089","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:45:53Z","timestamp":1774615553000},"page":"2089","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Electrochemical Detection of miR-29a and miR-34a Using AuNPs Immobilized by a Silsesquioxane Polyelectrolyte: Potential Early Alzheimer\u2019s Disease Biomarkers Detection"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4464-8567","authenticated-orcid":false,"given":"Amanda Loos Vargas","family":"Zinser","sequence":"first","affiliation":[{"name":"Department of Chemistry, State University of Ponta Grossa, Ponta Grossa CEP 84030-900, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6785-9843","authenticated-orcid":false,"given":"Felipe","family":"Zahrebelnei","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State University of Ponta Grossa, Ponta Grossa CEP 84030-900, PR, Brazil"},{"name":"Tel\u00eamaco Borba Campus, Federal Institute of Paran\u00e1, Tel\u00eamaco Borba CEP 84271-120, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5676-3993","authenticated-orcid":false,"given":"Jo\u00e3o Paulo","family":"Winiarski","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Federal University of Santa Catarina, Florian\u00f3polis CEP 88040-900, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Henrique de Souza","family":"Picciani","sequence":"additional","affiliation":[{"name":"Institute of Macromolecules, Federal University of Rio de Janeiro, Rio de Janeiro CEP 21941-901, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Wohnrath","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State University of Ponta Grossa, Ponta Grossa CEP 84030-900, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-5908","authenticated-orcid":false,"given":"Christiana Andrade","family":"Pess\u00f4a","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State University of Ponta Grossa, Ponta Grossa CEP 84030-900, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3233\/ADR-200171","article-title":"Alzheimer\u2019s Disease, Inflammation, and the Role of Antioxidants","volume":"4","author":"Sinyor","year":"2020","journal-title":"J. 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