Influence of Glucose Deprivation on Amyloid Beta Neurotoxicity

Alzheimer’s disease (AD) is a neurodegenerative disorder that is identified by cognitive decline, including memory loss and an impaired ability to perform daily, normal tasks, which leads to significant emotional, physical, and financial burdens for patients and caregivers. The main cause of AD is the accumulation of amyloid beta (Aβ) plaques, which disrupt neuronal function and cause disease progression. Glucose, the brain's primary energy source, plays a vital role in maintaining normal cognitive function. However, disruptions or issues in glucose metabolism are often developed in neurodegenerative diseases, including AD. This study explores the effects of glucose deprivation on amyloid beta neurotoxicity, and neuronal health in AD models, using SH-SY5Y neuroblastoma cells. The research investigates if glucose deprivation increases Aβ-induced neurotoxicity. SH-SY5Y cells were differentiated using retinoic acid (RA) and Phorbol-12-myristate-13-acetate (PMA) and exposed to varying glucose conditions along with varying concentrations of Aβ treatment. Cell viability and cytotoxicity were assessed using the Enzo LDH Assay, and the impact of glucose deprivation on Aβ cell death was measured. Though cytotoxic effects of Aβ on SH-SY5Y could be confirmed, results suggest that reduced glucose availability does not affect the intensity of neurodegenerative effects of Aβ. No statistically significant difference was observed in LDH release for the varying glucose concentrations in the presence of amyloid beta at 500 nM or 2 μM. This study aimed to enhance understanding of the connection between glucose metabolism and amyloid beta toxicity in Alzheimer's. A negative effect of glucose deprivation on Aβ cytotoxicity could not be established.