Abstract

Insights into Alzheimer’s Disease from NMR Metabolomics of Aß-expressing Drosophila

Anders Malmendal, Associate Professor, University of Copenhagen

The ability of our cells and tissues to retain proteins in their proper native conformation is impaired with age. The consequences of the proteostatic collapse in old age include a number of very common neurodegenerative disorders, the most prevalent of which is Alzheimers disease (AD). AD is characterised microscopically by the accumulation of two distinct protein amyloid deposits, extracellular neuritic plaques of the amyloid ß peptide (Aß), and the intracellular tangles composed of the tau protein. The use of a Drosophila Alzheimers disease (AD) model with its short life cycle and low maintenance costs allowed us to study the metabolite responses across all ages and to different Aß variants, all while avoiding vertebrate models. Both variants that affect performance and aging–mimicking AD toxicity, and those that affects neither, show distinct effects at the metabolite level, and the toxic effects were detected several days before symptoms were detected. Aß toxicity was associated with metabolite levels that are usually associated with older age, showing a potential to use metabolomics to measure physiological age. These results provide insight into the organisms protective response and to the toxic effects, and suggests biomarkers that can be used to assess the efficacy of therapeutic interventions.