Abstract
IntroductionThere 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.ObjectivesThe 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.MethodsTwenty 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.ResultsLevels 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.ConclusionIn conclusion, 4 bile acids may be useful to diagnose AD in plasma samples despite limitations in diagnostic accuracy.
Highlights
There is still a clear need for a widely available, inexpensive and reliable method to diagnose Alzheimer’s disease (AD) and monitor disease progression
Bile acids are of particular interest because they are the end product of the cholesterol metabolism, which directly link bile acids to AD as cholesterol has been implicated to play a role in progression of AD (Puglielli et al 2003)
In a follow up experiment, we demonstrated that lithocholic acid (LCA) levels significantly increased when healthy subjects converted to AD
Summary
There is still a clear need for a widely available, inexpensive and reliable method to diagnose Alzheimer’s disease (AD) and monitor disease progression. 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. Targeted metabolomic analysis in different laboratories including ours allowed to identify several lipid metabolites in plasma being suitable to differentiate AD patients from healthy controls (Mapstone et al 2014; Olazaran et al 2015; Klavins et al 2015). These preliminary data suggested that bile acids may be altered in AD (Olazaran et al 2015). In addition to the role in cholesterol elimination, bile acids exert effects on glucose and lipid metabolism via activation of bile acid receptors nuclear-farnesoid-X receptor (FXR) and G-protein-coupled plasma-membrane bound receptors (TGR5), directly linking bile acids with progression of AD with diabetes type II (Schilling 2016) or with cerebrovascular dysfunction (Humpel 2011b)
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