Bile acid quantification of 20 plasma metabolites identifies lithocholic acid as a putative biomarker in Alzheimer's disease.

Introduction: There is still a clear need for a widely available, inexpensive and reliable method to diagnose Alzheimer's disease (AD) and monitor disease progression. Liquid chromatography-mass spectrometry (LC-MS) is a powerful analytic technique with a very high sensitivity and specificity.

Objectives: The aim of the present study is to measure concentrations of 20 bile acids using the novel Kit from Biocrates Life Sciences based on LC-MS technique.

Methods: Twenty bile acid metabolites were quantitatively measured in plasma of 30 cognitively healthy subjects, 20 patients with mild cognitive impairment (MCI) and 30 patients suffering from AD.

Results: Levels of lithocholic acid were significantly enhanced in plasma of AD patients (50 ± 6 nM, p = 0.004) compared to healthy controls (32 ± 3 nM). Lithocholic acid plasma levels of MCI patients (41 ± 4 nM) were not significantly different from healthy subjects or AD patients. Levels of glycochenodeoxycholic acid, glycodeoxycholic acid and glycolithocholic acid were significantly higher in AD patients compared to MCI patients (p < 0.05). All other cholic acid metabolites were not significantly different between healthy subjects, MCI patients and AD patients. ROC analysis shows an overall accuracy of about 66%. Discriminant analysis was used to classify patients and we found that 15/23 were correctly diagnosed. We further showed that LCA levels increased by about 3.2 fold when healthy subjects converted to AD patients within a 8-9 year follow up period. Pathway analysis linked these changes to a putative toxic cholesterol pathway.

Conclusion: In conclusion, 4 bile acids may be useful to diagnose AD in plasma samples despite limitations in diagnostic accuracy.