Abstract
Clinical evidence has implicated diabetes mellitus as one of the risk factors for the development and progression of Alzheimer’s disease (AD). However, the neurotoxic pathway activated due to abnormalities in glucose metabolism has not yet been identified in AD. In order to investigate the relationship between impaired cerebral glucose metabolism and the pathophysiology of AD, SH-SY5Y human neuroblastoma cells were exposed to glyceraldehyde (GA), an inhibitor of glycolysis. GA induced the production of GA-derived advanced glycation end-products (GA-AGEs) and cell apoptosis, glycolytic inhibition, decreases in the medium concentrations of diagnostic markers of AD, such as amyloid β 1-42 (Aβ42), and increases in tau phosphorylation. These results suggest that the production of GA-AGEs and/or inhibition of glycolysis induce AD-like alterations, and this model may be useful for examining the pathophysiology of AD.
Highlights
Cerebrospinal fluid (CSF) tests have been proposed for the early detection of AD9
The reductions observed in cell viability following a 24 h incubation with GA were significantly restored by the addition of 1 mM (P < 0 .05) or 10 mM (P < 0 .01) acetoacetate (ACAC), a substrate for the tricarboxylic acid (TCA) cycle (Fig. 2d), whereas lactic acid concentrations were not (Fig. 2c)
2) The mechanism underlying GA-induced cell death involved the inhibition of glycolysis and concomitant induction of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). 3) Changes in the levels of Alzheimer’s disease (AD) biomarkers in GA-treated culture media were consistent with those in the CSF of AD patients
Summary
Cerebrospinal fluid (CSF) tests have been proposed for the early detection of AD9. there is currently no evidence to suggest that CSF findings in DM patients are an indicator AD. SH-SY5Y human neuroblastoma cells were treated with GA, an inhibitor of glycolysis[16,17], and examinations of cell viability and measurements of the concentrations of Aβ 42, total tau, and p-tauT181 proteins in culture media as well as the phosphorylation ratio of intracellular tau were performed in order to determine the involvement of glucose metabolism in the pathophysiology of AD.
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