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Katarina Fatur
Abstract
We investigate the link between the gut microbiome and cognitive decline in Alzheimer’s disease by identifying microbial metabolites associated with (compromised) brain health and examining metabolite changes in individuals who progress from a healthy state (NL) to mild cognitive impairment (MCI) and/or Alzheimer’s disease (AD).A dataset containing representative microbial metabolites in serum was obtained from the Alzheimer’s Disease Neuroimaging Initiative. A total of 104 metabolites were analyzed. These were collected over six years from 757 individuals. Kruskal-Wallis test was employed to assess the significance of serum differences among NL, MCI, and AD groups.Preliminary results: The MCI group is dominated by high levels of L-valine, β-alanine, cholic acid and valeric acid. NL controls exhibit the lowest levels of these metabolites and moderate levels of cholic acid and L-valine. The AD metabolite profile is marked by high deoxycholic and formic acid, while their amino acids are low.The results corroborate elevated formic acid as a biomarker for AD. MCI profile was characterized by oscillating metabolite levels, but further analysis is required to understand how metabolites of different groups change over time. Since the involved metabolites play crucial roles in biological processes such as inflammatory response, epigenetic mechanisms, and energy metabolism, their dysregulation has a complex association with the pathogenesis of AD. Understanding this relationship better would allow for early detection of individuals at risk, help identify microbial therapeutic targets, as well as serve as monitoring tool for disease progression and treatment response.