Dld-1 suppression attenuates the detrimental effects of amyloid beta deposition in a Caenorhabditis elegans model of Alzheimer’s disease

Abstract

Background Amyloid beta (Ab) aggregation is well studied as a major marker and determinant of Alzheimer’s disease (AD) pathology. While less work has been carried out on the role of energy metabolism in AD, there is good evidence that it also contributes to the disease. For example, low metabolic rate and ATP levels are also correlated with AD, which also extends to specific enzymes, metabolites, and proteins associated with glycolysis and the TCA cycle. Dihydrolipoamide dehydrogenase (DLD-1), the subject of this study, is a core metabolic enzyme with specific sequence variants that are associated with increased risk of late onset AD. DLD-1 contributes to four major metabolic multi-enzyme complexes, including a-ketoglutarate dehydrogenase (KGDH). A non-DLD subunit of KGDH also has variants that are associated with AD. Additionally, the activity level of the enzyme is significantly inversely correlated with the disease state in humans.