Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease.

INTRODUCTION: Late-onset Alzheimer's disease (LOAD) is a complex neurodegenerative disease characterized by multiple progressive stages, glucose metabolic dysregulation, Alzheimer's disease (AD) pathology, and inexorable cognitive decline. Discovery of metabolic profiles unique to sex, apolipoprotein E (APOE) genotype, and stage of disease progression could provide critical insights for personalized LOAD medicine. METHODS: Sex- and APOE-specific metabolic networks were constructed based on changes in 127 metabolites of 656 serum samples from the Alzheimer's Disease Neuroimaging Initiative cohort. RESULTS: Application of an advanced analytical platform identified metabolic drivers and signatures clustered with sex and/or APOE ɛ4, establishing patient-specific biomarkers predictive of disease state that significantly associated with cognitive function. Presence of the APOE ɛ4 shifts metabolic signatures to a phosphatidylcholine-focused profile overriding sex-specific differences in serum metabolites of AD patients. DISCUSSION: These findings provide an initial but critical step in developing a diagnostic platform for personalized medicine by integrating metabolomic profiling and cognitive assessments to identify targeted precision therapeutics for AD patient subgroups through computational network modeling.

[The role of Toll-like receptor 4 in acute pancreatitis].

OBJECTIVE: Toll-like receptors (TLRs) is a kind of pattern recognition receptor which widely exists on the cell membrane. It is a natural immune system component which can regulate the inflammatory response of the body participating in the signal transduction of cells and play an important role in the endogenous immune response. But the excessive inflammatory reaction initiated by TLRs can make the immune function of the body unbalanced and damage the function of many organs. The earliest discovered TLR4 is a transmembrane protein, almost express in all kinds of cell. Lots of study show it is closely related to the occurrence and development of acute pancreatitis (AP). The role and mechanism of TLR4 in AP will be reviewed in this article.