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

LCA-family bile acids are associated with amyloid-β status in patients across two independent cohorts.

• Two multimodal datasets were used: the Chinese Preclinical Alzheimer's Disease Study (n = 1397) and the Alzheimer's Disease Neuroimaging Initiative (n = 1275)
• LCA-family BAs showed consistent associations with amyloid-β status across both cohorts
• The study analyzed differences in BA levels and their associations with AD biomarkers using these combined datasets

Longitudinal changes in bile acid levels correlated with both amyloid and tau pathologies.

• The study examined longitudinal changes in BA levels in relation to AD biomarkers
• Correlations were observed with both amyloid pathology and tau pathology over time
• This longitudinal association suggests BAs track disease progression rather than representing only a cross-sectional marker

LCA and DCA family bile acids demonstrated predictive value with respect to AD pathology.

• Both LCA (lithocholic acid) and DCA (deoxycholic acid) families were evaluated for predictive capacity
• These bile acid families showed predictive value for AD pathology as identified through the multimodal dataset analyses
• LCA and DCA are metabolites produced by gut microbiota, linking gut microbiome activity to AD pathology

Imaging transcriptomic analyses suggested that bile acids modulate amyloid pathology through multiple mechanisms.

• Imaging transcriptomic analyses were employed to investigate the mechanistic basis of BA-amyloid associations
• The analyses indicated multiple, rather than a single, mechanisms by which BAs modulate amyloid pathology
• This multimodal approach combined neuroimaging data with transcriptomic information to infer mechanistic pathways

DCA- and LCA-family bile acids were proposed as molecular bridges connecting age signatures with AD pathology.

• The study identified DCA- and LCA-family BAs as intermediary molecules linking aging processes to AD pathology
• This positions these bile acids at the intersection of normal aging and neurodegenerative disease processes
• The finding suggests a mechanistic role for gut microbiota-derived metabolites in age-related AD risk

Alzheimer's disease involves early alterations in the gut microbiota that may impact brain function through the gut-brain axis.

• Bile acids are metabolites produced by the microbiota and may impact brain function through the gut-brain axis
• Early gut microbiota alterations are recognized as part of AD pathophysiology
• The study framed BA-AD associations within the context of the gut-brain axis as a mechanistic framework