Amyloid-β-Induced Neurotoxicity Modulates miR-98 and miR-200 Expression in SH-SY5Y Cells: A Step Toward Alzheimer’s Biomarker Discovery

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by abnormal protein accumulation, with no effective, non-invasive early diagnostic tools currently available. MicroRNAs (miRNAs), essential for neuronal survival and function, have been implicated in AD neuropathology. This study investigates the potential of miRNAs as biomarkers for AD by assessing the expression levels of miRNAs relevant to amyloid toxicity. An AD model was developed in SH-SY5Y human neuroblastoma cells with adequate Aβ42 expression to analyze the involvement of miRNAs in AD diagnosis. ELISA, MTT assays, and Congo red staining were utilized to quantify qualitative and quantitative amyloid formation. The expression of miRNAs and related genes, particularly those targeting APP and β-secretase, was measured using quantitative real-time PCR. Amyloid toxicity was successfully induced, and an increase in amyloid levels and significant changes in Alzheimer's related genes and targeted miRNAs were observed. Specifically, it was observed that miR-200a was upregulated and miR-98 was down-regulated in treated neuroblastoma cells. Notably, the altered expression patterns of these miRNAs showed a strong correlation with the pathological markers of AD, suggesting their potential as diagnostic indicators. Our findings enhance our understanding of AD mechanisms and offer insights into early diagnosis. Detecting AD in preclinical stages may enable earlier symptomatic intervention. In particular, dysregulation of certain miRNAs may play a role in neurodegenerative processes such as amyloid plaque formation in AD. miRNAs that respond to neurotoxic stimuli can be identified using in vitro models and confirmed by in vivo studies. These studies will help us understand both the development of noninvasive diagnostic tests and therapeutic approaches targeting miRNAs.