Caracterização metabólica de biomarcadores não invasivos circulantes relacionados à Doença de Alzheimer

Abstract

The life expectancy of the world's population has been increasing considerably, which leads to a growing concern about diseases in old age, such as Alzheimer's disease (AD). AD is defined as a slowly progressing disease, characterized by gradual neuronal loss, cognitive deficit, presence of amyloid plaques (AP) and neurofibrillary tangles (NFT). Before the development of AD itself, there is a prodromal phase called Minimal Cognitive Impairment (MCI). Metabolomics is a recent biological approach, through which the concentration of various metabolites present in biological samples can be measured. Changes between metabolic profiles may reflect differences in genetic background, epigenetic modifications, transcriptomic and proteomic aspects, diet, lifestyle, gut microbiota, stress, exposure to pathogens, medications, among others. In the present study, we aimed to identify non-invasive (urine) and less invasive (plasma) circulating biomarkers of the development and/or progression of late AD, through comparative metabolomics analysis by Nuclear Magnetic Resonance (NMR). To this end, 37 elderly people (>65 years old) were selected for voluntary participation in the study, 11 of whom were diagnosed with MCI, 12 diagnosed with late probable AD and 14 healthy elderly individuals. The comparative analysis between the groups showed metabolites with roles in energy metabolism, neuroprotective activity, neuromodulation, protein modulation, inflammation or pathological lesions, lipid and cholesterol metabolism, methionine metabolism, in addition to the influence of the gut microbiota. Circulating biomarkers associated with the development and progression of AD were found. Metabolic pathways were related to the altered compounds as well as genes previously related to the pathology. Gene variants without previous association with AD were also identified. The results obtained in this study suggest association between the altered compounds with the respective metabolic pathways where they exert their influence on the development and progression of the disease. The information acquired serves as a starting point for future research with better direction and greater depth.