6th Edition of Neurology World Conference 2026

Abstract

Background Alzheimer’s disease (AD) is characterized by progressive neurodegeneration and the accumulation of amyloid-β (Aβ). Stress experienced throughout life may alter glucocorticoid signaling and influence neuronal vulnerability. This study investigated whether hydrocortisone exposure alters Aβ-induced cytotoxicity in SH-SY5Y cells as an in vitro model to explore how stress-related glucocorticoid exposure may contribute to neuronal vulnerability and potentially influence the initiation or progression of AD-related neurodegenerative processes. Methods SH-SY5Y human neuroblastoma cells were maintained in DMEM supplemented with 10% fetal bovine serum and 0.5% penicillin–streptomycin at 37°C and 5% CO₂. Oligomeric Aβ was prepared from monomeric Aβ by dissolution in DMSO, dilution in serum-free medium, and incubation at 4°C for 24 h. Cells were pretreated with hydrocortisone (HC) for different durations before exposure to varying concentrations of oligomeric Aβ for 24 h. Cell viability was assessed using the MTT assay and expressed as fold change relative to the corresponding control. Three independent experiments were performed in triplicate. Data were analyzed using one-way ANOVA followed by Tukey’s multiple-comparisons test, with p < 0.05 considered statistically significant. Results The effect of hydrocortisone (HC) on Aβ-induced cytotoxicity varied with both Aβ concentration and HC pretreatment duration. At lower Aβ concentrations, HC pretreatment did not significantly alter Aβ-induced cytotoxicity across the tested time intervals. In contrast, at higher Aβ concentrations, the shortest HC pretreatment interval was associated with significantly reduced cell viability and increased Aβ-induced cytotoxicity, whereas longer pretreatment intervals produced no significant effects. These findings indicate that the effect of HC on cellular vulnerability to Aβ is dependent on both Aβ concentration and the duration of HC exposure. Conclusion Further investigation is needed to elucidate the molecular mechanisms by which glucocorticoid signaling influences Aβ-associated neurotoxicity. Understanding this relationship may provide insight into how stress-related glucocorticoid exposure throughout life contributes to neuronal vulnerability and may help clarify its potential role in the initiation and progression of Alzheimer’s disease.