ABSTRACT Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with mild cognitive impairment (MCI) as its critical prodromal stage. Identifying reliable biomarkers to distinguish AD from MCI is key for early intervention. This study explored miR‐769‐5p's potential as a diagnostic biomarker for AD and its mechanism, especially its links to oxidative stress and target gene CREB5 . Serum miR‐769‐5p and CREB5 levels were measured via qRT‐PCR. Cellular models used Aβ₄₂‐treated SH‐SY5Y cells, validated by confirming key AD pathologies including increased Tau phosphorylation. Functional/mechanistic assessments employed CCK‐8, MDA, SOD, and dual‐luciferase reporter assays. Clinically, multivariate logistic regression identified miR‐769‐5p as a strong independent protective factor (OR = 0.029, p < 0.001). miR‐769‐5p was downregulated in AD versus MCI and accurately distinguished them (AUC = 0.919). In Aβ‐treated cells, miR‐769‐5p overexpression reduced Aβ‐induced proliferation suppression and oxidative stress (lower MDA, higher SOD, all p < 0.01), while inhibition worsened damage. CREB5 , a direct miR‐769‐5p target, was upregulated in AD. Functionally, rescue assays confirmed CREB5 overexpression reversed miR‐769‐5p mimic's protection. In conclusion, serum miR‐769‐5p is a promising biomarker for AD‐MCI distinction and may protect against AD by targeting CREB5 to mitigate oxidative stress.
Ma et al. (Fri,) studied this question.