Browsing by Subject "Apolipoprotein E ε4"

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    APOE-ε4 is associated with earlier symptom onset in LOAD but later symptom onset in EOAD
    (Wiley, 2023) Polsinelli, Angelina J.; Lane, Kathleen A.; Manchella, Mohit K.; Logan, Paige E.; Gao, Sujuan; Apostolova, Liana G.; Neurology, School of Medicine
    Background: We studied the effect of apolipoprotein E (APOE) ε4 status and sex on age of symptom onset (AO) in early- (EO) and late- (LO) onset Alzheimer's disease (AD). Method: A total of 998 EOAD and 2562 LOAD participants from the National Alzheimer's Coordinating Center (NACC) were included. We used analysis of variance to examine AO differences between sexes and APOE genotypes and the effect of APOE ε4, sex, and their interaction on AO in EOAD and LOAD, separately. Results: APOE ε4 carriers in LOAD had younger AO and in EOAD had older AO. Female EOAD APOE ε4 carriers had older AO compared to non-carriers (P < 0.0001). There was no difference for males. Both male and female LOAD APOE ε4 carriers had younger AO relative to non-carriers (P < 0.0001). Conclusion: The observed earlier AO in EOAD APOE ε4 non-carriers relative to carriers, particularly in females, suggests the presence of additional AD risk variants.
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    Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease
    (Wiley, 2023) Chang, Rui; Trushina, Eugenia; Zhu, Kuixi; Zaidi, Syed Shujaat Ali; Lau, Branden M.; Kueider-Paisley, Alexandra; Moein, Sara; He, Qianying; Alamprese, Melissa L.; Vagnerova, Barbora; Tang, Andrew; Vijayan, Ramachandran; Liu, Yanyun; Saykin, Andrew J.; Brinton, Roberta D.; Kaddurah-Daouk, Rima; Alzheimer’s Disease Neuroimaging Initiative; Alzheimer’s Disease Metabolomics Consortium; Radiology and Imaging Sciences, School of Medicine
    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.