Abstract:

Objective

The study aims to evaluate the potential clinical application of combined 15 bile acids （BAs） using liquid chromatography-tandem mass spectrometry （LC-MS/MS） and 17 trace elements using inductively coupled plasma mass spectrometry （ICP-MS） in the auxiliary predictive diagnosis of Alzheimer's disease （AD）.

Methods

A total of 72 patients diagnosed with AD in the Neurology and Cognitive Disorder Departments of the Third affiliated Hospital of Shenzhen University from 2021 to 2022 were enrolled in the AD group， and 70 healthy individuals undergoing physical examinations during the same period were included as the control group. Quantification of 15 BAs in serum was performed using LC-MS/MS， while 17 trace elements in whole blood were quantified using ICP-MS. The differences in BAs and trace element levels between AD patients and healthy controls were compared. Logistic regression models were constructed for combined diagnostic analysis， and receiver operating characteristic （ROC） curves were plotted to evaluate the diagnostic value of these biomarkers in AD.

Results

Methodological validation confirmed that the analytical performance of LC-MS/MS and ICP-MS met the stringent standards required by the assay kits. In the biomarker analysis comparing AD group and healthy controls， significantly lower levels of lithocholic acid （LCA）， ferrum （Fe）， and strontium （Sr）were observed in AD group （P＜0.05）. Conversely， levels of magnesium （Mg）， calcium （Ca）， manganese（Mn）， copper （Cu）， selenium （Se）， and lithium （Li） were significantly higher in AD patients （P＜0.05）.The combined diagnostic model of LCA with Fe and Sr demonstrated good predictive ability， with an area under the curve （AUC） of 0.82， sensitivity of 93.8%， and specificity of 56.1%. Another model combining Mg， Ca， Mn， Cu， and Se also exhibited good predictive performance， with an AUC of 0.80， sensitivity of 83.3%， and specificity of 68.3%.

Conclusion

This study reveals significant imbalances in BAs and trace elements in patients with AD， particularly the decreased levels of LCA， Fe， and Sr， and the increased levels of Mg， Ca， Mn， Cu， and Se. These changes have the potential to serve as predictive biomarkers for AD， providing new insights into the biological pathways involved in the disease and offering potential avenues for early diagnosis.

Key words: Alzheimer's disease, bile acid, trace element, LC-MS/MS, ICP-MS