Bile acids are associated with baseline and longitudinal amyloid and tau pathology in patients with Alzheimer's disease

INTRODUCTION: Alzheimer's disease (AD), a neurodegenerative disease, involves early alterations in the gut microbiota. Bile acids (BAs), which are metabolites produced by the microbiota, may impact brain function through the gut-brain axis. METHODS: By reference to multimodal datasets from the Chinese Preclinical Alzheimer's Disease Study (n = 1397) and the Alzheimer's Disease Neuroimaging Initiative (n = 1275), we analyzed differences in BA levels and their associations with AD biomarkers. RESULTS: Lithocholic acid (LCA) -family BAs are associated with the amyloid-β status. Longitudinal changes in BA levels correlated with amyloid and tau pathologies. LCA and the deoxycholic acid (DCA) family exhibited predictive value with respect to AD pathology. Imaging transcriptomic analyses suggested that BAs modulated amyloid pathology through multiple mechanisms. DISCUSSION: DCA- and LCA-family BAs were proposed as molecular bridges that connect age signatures with AD pathology. They represent a new avenue for the development of biomarkers and therapeutic interventions.