{"doi":"10.1002/alz.12675","title":"Predictive metabolic networks reveal sex‐ and <i>APOE</i> genotype‐specific metabolic signatures and drivers for precision medicine in Alzheimer's disease","abstract":"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.","journal":"Alzheimer s & Dementia","year":2022,"id":239730,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":107434,"name":"Eugenia Trushina","orcid":"0000-0002-6291-2860","position":1,"is_corresponding":false},{"id":371567,"name":"Kuixi Zhu","orcid":"0000-0003-4361-1138","position":2,"is_corresponding":false},{"id":865963,"name":"Syed Shujaat Ali Zaidi","orcid":"0000-0003-3178-2466","position":3,"is_corresponding":false},{"id":866744,"name":"Branden M Lau","orcid":null,"position":4,"is_corresponding":false},{"id":244566,"name":"Alexandra Kueider‐Paisley","orcid":"0000-0001-7132-5003","position":5,"is_corresponding":false},{"id":372852,"name":"Sara Moein","orcid":null,"position":6,"is_corresponding":false},{"id":866745,"name":"Qianying He","orcid":null,"position":7,"is_corresponding":false},{"id":371569,"name":"Melissa Alamprese","orcid":"0000-0002-5290-1789","position":8,"is_corresponding":false},{"id":866746,"name":"Barbora Vagnerova","orcid":null,"position":9,"is_corresponding":false},{"id":107856,"name":"Andrew Tang","orcid":null,"position":10,"is_corresponding":false},{"id":865964,"name":"Ramachandran Vijayan","orcid":"0000-0001-5788-5282","position":11,"is_corresponding":false},{"id":743933,"name":"Yan‐Yun Liu","orcid":null,"position":12,"is_corresponding":false},{"id":27595,"name":"Andrew J. Saykin","orcid":"0000-0002-1376-8532","position":13,"is_corresponding":false},{"id":77490,"name":"Roberta Dı́az Brinton","orcid":"0000-0001-8450-772X","position":14,"is_corresponding":false},{"id":75183,"name":"Rima Kaddurah‐Daouk","orcid":"0000-0003-1858-5732","position":15,"is_corresponding":false},{"id":244572,"name":"Rui Chang","orcid":"0000-0001-7950-8920","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T00:22:41.699779Z","pmid":"35481667","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}