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.

Mechanism of two styryl BODIPYs as fluorescent probes and protective agents in lipid bilayers against aqueous ClO.

Two styryl BODIPY derivatives, BOH and BOE, with different hydrophilic properties, were investigated for their reaction mechanisms in lipid bilayers against aqueous ClO-, by both experimental and theoretical methods. Density functional theory (DFT) calculations confirmed their identical conformations in solution. Fluorescence spectra and high-resolution mass spectra corroborated the central vinyl group as a common antioxidation moiety against ClO- oxidation. In giant unilamellar vesicles (GUVs), distinct reaction kinetics with ClO- suggested that BOE provided superior protective effects compared to BOH on lipids. Molecular dynamics simulations indicated that the lipophilic octyloxy group in BOE led to its deeper localization within the lipid phase, bringing it closer to the corresponding lipid target group. This study establishes the two styryl BODIPYs as promising fluorescent probes for detecting aqueous ClO- in lipid-water polyphasic systems.