Chang, RuiTrushina, EugeniaZhu, KuixiZaidi, Syed Shujaat AliLau, Branden M.Kueider-Paisley, AlexandraMoein, SaraHe, QianyingAlamprese, Melissa L.Vagnerova, BarboraTang, AndrewVijayan, RamachandranLiu, YanyunSaykin, Andrew J.Brinton, Roberta D.Kaddurah-Daouk, RimaAlzheimer’s Disease Neuroimaging InitiativeAlzheimer’s Disease Metabolomics Consortium2024-02-282024-02-282023Chang R, Trushina E, Zhu K, et al. Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease. Alzheimers Dement. 2023;19(2):518-531. doi:10.1002/alz.12675https://hdl.handle.net/1805/38964Introduction: 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.en-USPublisher PolicyAlzheimer's Disease Neuroimaging InitiativeApolipoprotein E ε4Computational systems biologyLate-onset Alzheimer's diseaseMetabolic biomarkersMetabolic networkMetabolomicsPrecision medicineSex-specific metabolic changesArticle