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

Publication ,  Journal Article
Chang, R; Trushina, E; Zhu, K; Zaidi, SSA; Lau, BM; Kueider-Paisley, A; Moein, S; He, Q; Alamprese, ML; Vagnerova, B; Tang, A; Vijayan, R ...
Published in: Alzheimers Dement
February 2023

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.

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Published In

Alzheimers Dement

DOI

EISSN

1552-5279

Publication Date

February 2023

Volume

19

Issue

2

Start / End Page

518 / 531

Location

United States

Related Subject Headings

  • Precision Medicine
  • Neurodegenerative Diseases
  • Metabolic Networks and Pathways
  • Male
  • Humans
  • Geriatrics
  • Genotype
  • Female
  • Apolipoproteins E
  • Apolipoprotein E4
 

Citation

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Chicago
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Chang, R., Trushina, E., Zhu, K., Zaidi, S. S. A., Lau, B. M., Kueider-Paisley, A., … Alzheimer’s Disease Neuroimaging Initiative† and the Alzheimer’s Disease Metabolomics Consortium, . (2023). Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease. Alzheimers Dement, 19(2), 518–531. https://doi.org/10.1002/alz.12675
Chang, Rui, Eugenia Trushina, Kuixi Zhu, Syed Shujaat Ali Zaidi, Branden M. Lau, Alexandra Kueider-Paisley, Sara Moein, et al. “Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease.Alzheimers Dement 19, no. 2 (February 2023): 518–31. https://doi.org/10.1002/alz.12675.
Chang R, Trushina E, Zhu K, Zaidi SSA, Lau BM, Kueider-Paisley A, 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 Feb;19(2):518–31.
Chang, Rui, et al. “Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease.Alzheimers Dement, vol. 19, no. 2, Feb. 2023, pp. 518–31. Pubmed, doi:10.1002/alz.12675.
Chang R, Trushina E, Zhu K, Zaidi SSA, Lau BM, Kueider-Paisley A, Moein S, He Q, Alamprese ML, Vagnerova B, Tang A, Vijayan R, Liu Y, Saykin AJ, Brinton RD, Kaddurah-Daouk R, Alzheimer’s Disease Neuroimaging Initiative† and the Alzheimer’s Disease Metabolomics Consortium. Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease. Alzheimers Dement. 2023 Feb;19(2):518–531.
Journal cover image

Published In

Alzheimers Dement

DOI

EISSN

1552-5279

Publication Date

February 2023

Volume

19

Issue

2

Start / End Page

518 / 531

Location

United States

Related Subject Headings

  • Precision Medicine
  • Neurodegenerative Diseases
  • Metabolic Networks and Pathways
  • Male
  • Humans
  • Geriatrics
  • Genotype
  • Female
  • Apolipoproteins E
  • Apolipoprotein E4