What Are the Reliable Plasma Biomarkers for Mild Cognitive Impairment? A Clinical 4D Proteomics Study and Validation.

Objective: At present, Alzheimer's disease (AD) lacks effective treatment means, and early diagnosis and intervention are the keys to treatment. Therefore, for mild cognitive impairment (MCI) and AD patients, blood sample analysis using the 4D nonstandard (label-free) proteomic in-depth quantitative analysis, looking for specific protein marker expression differences, is important. These marker levels change as AD progresses, and the analysis of these biomarkers changes with this method, which has the potential to show the degree of disease progression and can be used for the diagnosis and preventive treatment of MCI and AD. Materials and Methods: Patients were recruited according to the inclusion and exclusion criteria and divided into three groups according to scale scores. Elderly patients diagnosed with AD were selected as the AD group (n = 9). Patients diagnosed with MCI were classified into the MCI group (n = 10). Cognitively healthy elderly patients were included in the normal cognition control group (n = 10). Patients' blood samples were used for 4D label-free proteomic in-depth quantitative analysis to identify potential blood biomarkers. The sample size of each group was expanded (n = 30), and the selected biomarkers were verified by enzyme-linked immunosorbent assay (ELISA) to verify the accuracy of the proteomic prediction. Results: Six specific blood markers, namely, APOE, MMP9, UBR5, PLA2G7, STAT5B, and S100A8, were detected by 4D label-free proteomic quantitative analysis. These markers showed a statistically significant upregulation trend in the MCI and AD groups compared with the normal cognition control group (P < 0.05). ELISA results showed that the levels of these six proteins in the MCI group were significantly higher than those in the normal cognition control group, and the levels of these six proteins in the AD group were significantly higher than those in the MCI group (P < 0.05). Conclusion: The plasma levels of APOE, MMP9, UBR5, PLA2G7, STAT5B, and S100A8 in cognitively healthy elderly patients and patients with MCI and AD were significantly different and, more importantly, showed a trend of increasing expression. These results indicate that these six human plasma markers have important diagnostic and therapeutic potential in the identification of cognitive impairment and have value for in-depth research and clinical application.

Lipidomic characterisation discovery for coronary heart disease diagnosis based on high-throughput ultra-performance liquid chromatography and mass spectrometry.

Although many diagnostic tools have been developed for coronary heart disease (CHD), its diagnosis is still challenging. Lipids play an important role in diseases and a lipidomics approach could offer a platform to clarify the pathogenesis and pathologic changes of this disease. To the best of our knowledge, no lipidomics studies on serum have been attempted to improve the diagnosis and identify the potential biomarkers of CHD. The aim of this study was to investigate the distinctive lipid changes in serum samples of CHD patients and to identify candidate biomarkers for the reliable diagnosis of CHD using this platform. In this study, the serum lipid profiles of CHD patients were measured via ultra-performance liquid chromatography-G2-Si-high definition mass spectrometry combined with multivariate data analysis. A MetaboAnalyst tool was used for the analysis of the receiver operating-characteristic, while the IPA software was applied for the pathway analysis. The obtained results inferred that 33 lipid molecular species involving 6 fatty acids, 21 glycerophospholipids and 6 sphingolipids have significant differences in the serum of CHD patients. Simultaneously, 4 upstream regulatory proteins related to lipid metabolism disorders of CHD were predicted. Ten lipids have high clinical diagnostic significance according to the receiver operating-characteristic curves. This research shows that the in-depth study of lipids in the serum contributes to the clinical diagnosis of CHD and interprets the occurrence and development of CHD.