| Abstrakt: |
Background: Alzheimer's disease (AD) is an aging‐related neurodegenerative disease, leading to the progressive loss of memory and other cognitive functions. As there is still no cure for AD, the growth in the number of susceptible individuals represents a major emerging threat to public health. Current AD diagnosis methods can only identify patients in the advanced stage of the disease, that means when the dementia is already present. This highlights the need for new approaches for the diagnosis of AD at earlier stages, especially before the symptoms appear. In addition, AD is reported to be closely linked with abnormal lipid metabolism. The objective of this study is to identify blood‐based lipid biomarkers to gain a more comprehensive understanding of what causes AD and its subsequent development. Method: A longitudinal study with 4 different ages (12 weeks, 25 weeks, 50 weeks, and 85 weeks) was conducted in TgF344 transgenic (AD) and wild‐type (WT) rats. Metabolomics profiling of EDTA plasma yielded 811 metabolites after quality control. Metabolites profiled included medium and apolar lipids covering 27 lipid classes, signaling lipids including oxylipins, isoprostanes, eicosanoids, bile acids, endocannabinoids. All data was log2 transformed. All statistical analysis and visualizations were performed in R. Result: The sphingomyelins (SM) were decreased at 25 weeks with AD having more SM expressed than the WT group, while this was reversed at 50 weeks. In 12 weeks, the volcano plot of AD/WT showed more significant lipids on female (p<0.05:15) than male (p<0.05:2). Whereas, in 25 weeks, male (p<0.05:56) showed more significant lipids than female (p<0.05:7). The ratios of an eicosanoid to its seven products were first decreased, then increased over time in both WT and AD group. However, the WT group reached its minimum at 50 weeks, while the AD group reached its minimum at 25 weeks. Sex differences were found in AD/WT among all ages. Conclusion: Lipidomics data on longitudinal course of potential lipid biomarkers in plasma of WT and AD rats show some effects of AD and/or aging. It is anticipated that this information will contribute to developing lipid biomarker fingerprints for diagnosis and monitoring AD progression distinct from normal aging. [ABSTRACT FROM AUTHOR] |
