Relationship between Plasma Lipid Profile and Cognitive Status in Early Alzheimer Disease.

Alzheimer disease (AD) is a heterogeneous and complex disease in which different pathophysiological mechanisms are involved. This heterogenicity can be reflected in different atrophy patterns or clinical manifestations. Regarding biochemical pathways involved in early AD, lipid metabolism plays an important role; therefore, lipid levels have been evaluated as potential AD diagnosis biomarkers, and their levels could be related to different AD clinical manifestations. Therefore, the aim of this work is to study AD lipid profiles from early AD patients and evaluate their clinical significance. For this purpose, untargeted plasma lipidomic analysis was carried out in early AD patients (n = 31) diagnosed with cerebrospinal fluid (CSF) biomarkers. Cluster analysis was carried out to define early AD subgroups according to the lipid levels. Then, the clinical significance of each lipid profile subgroup was studied, analyzing differences for other variables (cognitive status, CSF biomarkers, medication, comorbidities, age, and gender). The cluster analysis revealed two different groups of AD patients. Cluster 1 showed higher levels of plasma lipids and better cognitive status than Cluster 2. However, no differences were found for the other variables (age, gender, medication, comorbidities, cholesterol, and triglycerides levels) between both groups. Plasma lipid levels could differentiate two early AD subgroups, which showed different cognitive statuses. However, further research with a large cohort and longitudinal study evaluating the clinical evolution of these patients is required. In general, it would involve a relevant advance in the knowledge of AD pathological mechanisms, potential treatments, and precision medicine.

Optimized derivatization of primary amines with the fluorogenic reagent naphthalene-2,3-dicarboxaldehyde toward reproducible quantitative analysis in biological systems.

Primary amines are the target of many bioanalytical analyses, as they are ubiquitous in biological systems and responsible for numerous important processes including neurotransmission and cell signaling. Primary amines can be sensitively detected via fluorescence after their reaction with the fluorogenic reagent naphthalene-2,3-dicarboxaldehyde (NDA) in the presence of cyanide through the formation of fluorescent N-substituted 1-cyanobenz[f]isoindole (CBI) derivatives. While fluorogenic reagents such as NDA can be advantageous for sensitive detection, improvements in both long-term stability and speed of reaction are necessary to enable practical and reproducible quantitative analysis. In this work, various CBI-amines were interrogated for their fluorescence characteristics over time under previously reported conditions (75:25 aqueous buffer:acetonitrile). An amine-specific decline in fluorescence and delay to reach maximum fluorescence were observed. Based on structural characteristics, we hypothesized that these effects were due to the solvents employed enabling analyte intermolecular interactions that resulted in fluorescence quenching over time. To mitigate fluorescence-quenching intermolecular interactions, we developed two strategies to improve the fluorescence of the CBI-product over long time periods: (1) the addition of the complexation reagent ß-cyclodextrin to the reaction matrix and (2) the substitution of acetonitrile with dimethyl sulfoxide. Both strategies improved fluorescence stability over time, and the incorporation of dimethyl sulfoxide also enabled more rapid attainment of maximum fluorescence and a higher absolute fluorescence when compared to initial conditions. When employed in combination, these two approaches further improve fluorescence stability over time for the most hydrophobic analytes. In the future, these strategies can be employed for the practical and reproducible quantitative analysis of primary amines in biological systems, including those related to neurological disorders and disease states.