Serum bile acids improve prediction of Alzheimer’s progression in a sex-dependent manner

Abstract INTRODUCTION There is evidence that there are differences in the serum levels of bile acids (BAs) in males and females and their risk of developing Alzheimer’s disease (AD). We previously reported that serum BAs are associated with AD. It remains unclear, however, how changes in serum BAs may relate to the development of AD in a sex-dependent manner. METHODS We analyzed 33 BAs in the sera of 4219 samples from 1180 subjects in the ADNI cohort. Using linear models, we examined the associations between BAs and mild cognitive impairment (MCI) progression and clinical markers. RESULTS Significant alterations in BA profiles occurred at an early stage of MCI and were associated with the onset and progression of MCI. These changes were more dramatic in men than in women. BA markers improved the ability of current clinical markers to diagnose MCI and predict its progression. DISCUSSION Our results highlight the role of BAs in the development of AD and may help improve AD prediction and personalized therapies. Research in context Systematic review: We examined the relationship between bile acid (BA), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). We previously reported this association. Our findings were consistent with those of other studies, although previous research did not consider sex differences or comprehensively evaluate the potential of BAs as diagnostic markers for AD. Interpretation : Our results suggest that changes in BA profiles may play a role in the development of AD and that sex-specific differences may be important for personalized prediction and management of the disease. Future directions : In the future, it will be important to confirm our findings with other independent samples and further investigate the ways in which BA metabolism, including cholesterol catabolism in the liver and brain, may contribute to AD.