{"doi":"10.1002/alz.13130","title":"Large‐scale proteome and metabolome analysis of CSF implicates altered glucose and carbon metabolism and succinylcarnitine in Alzheimer's disease","abstract":"INTRODUCTION: A hallmark of Alzheimer's disease (AD) is the aggregation of proteins (amyloid beta [A] and hyperphosphorylated tau [T]) in the brain, making cerebrospinal fluid (CSF) proteins of particular interest. METHODS: We conducted a CSF proteome-wide analysis among participants of varying AT pathology (n = 137 participants; 915 proteins) with nine CSF biomarkers of neurodegeneration and neuroinflammation. RESULTS: ). Proteins from glucose and carbon metabolism pathways were enriched among amyloid- and tau-associated proteins, including malate dehydrogenase and aldolase A, whose associations with tau were replicated in an independent cohort (n = 717). CSF metabolomics identified and replicated an association of succinylcarnitine with phosphorylated tau and other biomarkers. DISCUSSION: These results implicate glucose and carbon metabolic dysregulation and increased CSF succinylcarnitine levels with amyloid and tau pathology in AD. HIGHLIGHTS: Cerebrospinal fluid (CSF) proteome enriched for extracellular, neuronal, immune, and protein processing. Glucose/carbon metabolic pathways enriched among amyloid/tau-associated proteins. Key glucose/carbon metabolism protein associations independently replicated. CSF proteome outperformed other omics data in predicting amyloid/tau positivity. CSF metabolomics identified and replicated a succinylcarnitine-phosphorylated tau association.","journal":"Alzheimer s & Dementia","year":2023,"id":321209,"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":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7973,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":817827,"name":"Justin McKetney","orcid":"0000-0002-2405-8288","position":1,"is_corresponding":false},{"id":265268,"name":"Yuetiva Deming","orcid":null,"position":2,"is_corresponding":false},{"id":817828,"name":"Autumn Morrow","orcid":"0000-0002-2301-9869","position":3,"is_corresponding":false},{"id":763250,"name":"Gilda E. Ennis","orcid":"0000-0003-4329-0215","position":4,"is_corresponding":false},{"id":289689,"name":"Erin M. Jonaitis","orcid":"0009-0004-5091-8255","position":5,"is_corresponding":false},{"id":536174,"name":"Carol A. Van Hulle","orcid":"0000-0002-2288-8819","position":6,"is_corresponding":false},{"id":17613,"name":"Chengran Yang","orcid":"0000-0003-4577-5590","position":7,"is_corresponding":false},{"id":337940,"name":"Yun Ju Sung","orcid":"0000-0002-8021-4070","position":8,"is_corresponding":false},{"id":767175,"name":"Muhammad Ali","orcid":"0000-0002-1399-6631","position":9,"is_corresponding":false},{"id":671639,"name":"Gwendlyn Kollmorgen","orcid":null,"position":10,"is_corresponding":false},{"id":763251,"name":"Ivonne Suridjan","orcid":"0000-0002-1803-9515","position":11,"is_corresponding":false},{"id":818514,"name":"Anna Bayfield","orcid":null,"position":12,"is_corresponding":false},{"id":291168,"name":"Barbara B. Bendlin","orcid":"0000-0002-0580-9875","position":13,"is_corresponding":false},{"id":27601,"name":"Henrik Zetterberg","orcid":"0000-0003-3930-4354","position":14,"is_corresponding":false},{"id":27600,"name":"Kaj Blennow","orcid":"0000-0002-1890-4193","position":15,"is_corresponding":false},{"id":230680,"name":"Carlos Cruchaga","orcid":"0000-0002-0276-2899","position":16,"is_corresponding":false},{"id":289694,"name":"Cynthia M. Carlsson","orcid":"0000-0001-5743-1563","position":17,"is_corresponding":false},{"id":230038,"name":"Sterling C. Johnson","orcid":"0000-0002-8501-545X","position":18,"is_corresponding":false},{"id":289695,"name":"Sanjay Asthana","orcid":"0000-0002-3998-4479","position":19,"is_corresponding":false},{"id":71208,"name":"Joshua J. Coon","orcid":"0000-0002-0004-8253","position":20,"is_corresponding":false},{"id":261840,"name":"Corinne D. Engelman","orcid":"0000-0003-4750-5607","position":21,"is_corresponding":false},{"id":556967,"name":"Daniel J. Panyard","orcid":"0000-0001-5480-4803","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-19T01:07:32.611759Z","pmid":"37218097","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":[]}