Since CSF is already collected for AD diagnosis, further investigation into the small molecule signatures (e.g., via metabolomics and exposomics) could provide new insights to better understand disease progression and identify individuals at risk. CSF is the closest biological fluid to the brain, such that abnormalities in this matrix are directly related to pathological changes in the brain . Despite its biological significance, the number of metabolomics/exposomics studies in CSF samples remains low. This due to the invasive and thus precious nature of the sample (requiring lumbar puncture) combined with methodological challenges, including the lack of standard material , and the relatively low chemical concentrations in CSF compared to other matrices like blood . Previous studies have revealed that alterations in various metabolomics pathways are associated with AD and MCI, including the energy metabolism, fatty acid oxidation, amino acids, and lipid biosynthesis . Recently, bile acids (BAs) were proposed to be involved in the AD pathogenesis have not yet been explored in CSF in the context of MCI and AD.