MicroRNA Signatures in Alzheimer’s Disease and Normal-Tension Glaucoma: A Comparative Expression Analysis of miR-128 and miR-455-3p

INTRODUCTION: The relationship between Alzheimer's disease (AD) and normal-tension glaucoma (NTG) is an emerging area of interest owing to shared neurodegenerative features. Nevertheless, few studies have ascertained circulating microRNAs (miR) across both conditions. This study aimed to compare the expression of miR-128 and miR-455-3p in patients with NTG and AD and in controls, and to explore their potential as circulating biomarker candidates. MATERIALS AND METHODS: In this cross-sectional study, serum miRNAs were extracted using a column- based kit and quantified by SYBR Green qRT-PCR (normalized to U6). Each reaction was run in triplicate. Data were analyzed via ANCOVA adjusted for age and sex, followed by Bonferroni post-hoc tests. RESULTS: Both miR-128 and miR-455-3p were significantly upregulated in the AD and NTG groups compared with controls (p < 0.001 for both). Adjusted mean expression for miR-128 was approximately 2.1 in AD, 2.6 in NTG, and 0.3 in controls, while the corresponding miR-455-3p values were 2.9, 3.1, and 0.8, respectively. Post-hoc comparisons confirmed higher expression in both disease groups compared with controls, but not between AD and NTG. Power analysis revealed >0.99 power for group comparisons with controls, consistent with robust group-level differences. DISCUSSION: miR-128 and miR-455-3p are implicated in neuronal stress responses, mitochondrial regulation, and amyloid-beta processing. Their parallel upregulation in AD and NTG suggests overlapping molecular signatures and may reflect systemic responses to neurodegenerative stress. These findings are also consistent with growing evidence that the eye and brain share vulnerability to similar cellular processes in neurodegeneration. CONCLUSION: Elevated serum miR-128 and miR-455-3p in both AD and NTG indicate overlapping expression profiles across conditions. These miRNAs may serve as promising circulating biomarker candidates and support the concept of a molecular interplay between ocular and cerebral pathologies. However, their diagnostic and mechanistic potential warrants validation in largescale, longitudinal studies.