Introduction: Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimers disease (AD) including neuroinflammation and amyloid-beta deposition. Method: Serum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n=1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the A/T/N (Amyloid, Tau and Neurodegeneration) biomarkers for AD: CSF biomarkers, atrophy (MRI), and brain glucose metabolism ([18F]FDG-PET). Results: Of 23 BA and relevant calculated ratios, three BA signatures were associated with CSF Aβ1-42 (A) and three with CSF p-tau181 (T) (corrected p<0.05). Furthermore, three, twelve, and fourteen BA signatures were associated with CSF t-tau, glucose metabolism, and atrophy (N), respectively (corrected p<0.05). Conclusion: This is the first study to show serum-based BA metabolites are associated with A/T/N AD biomarkers, providing further support for a role of BA pathways in AD pathophysiology. Prospective clinical observations and validation in model systems are needed to assess causality and specific mechanisms underlying this association.

Altered Bile Acid Profile in Mild Cognitive Impairment and Alzheimer's Disease: Relationship to Neuroimaging and CSF Biomarkers