{"doi":"10.1101/2022.08.14.503929","title":"Dietary choline intake is necessary to prevent systems-wide organ pathology and reduce Alzheimer’s disease hallmarks","abstract":"Abstract Evidence suggests that environmental factors may contribute to Alzheimer’s disease (AD). The B-like vitamin choline plays key roles in body- and brain-related functions. Choline produced endogenously by the phosphatidylethanolamine N-methyltransferase (PEMT) enzyme in the liver is not sufficient for adequate physiological functions, necessitating daily dietary intake. ∼90% of Americans don’t reach the recommended daily choline intake. Thus, it’s imperative to determine whether dietary deficiency increases disease outcomes. Here, we placed 3xTg-AD, a model of AD, and non-transgenic (NonTg) control mice on either a sufficient choline (ChN) or choline deficient (Ch-; choline deficiency) diet from 3 to 12 (early to late adulthood) months of age. Ch- reduced plasma choline and acetylcholine levels, increased weight, and impaired both glucose metabolism and motor function in NonTg, with 3xTg-AD mice showing greater deficits. Tissue analyses showed cardiac and liver pathology, and elevated Amyloid-β and phosphorylated tau in the hippocampus and cortex of 3xTg-AD Ch- mice. Unbiased proteomic analyses revealed Ch- altered hippocampal networks associated with microtubule function and postsynaptic membrane regulation. In plasma, Ch- altered protein networks associated with insulin metabolism, mitochondrial function, and inflammation. Collectively, our data highlight that dietary choline intake is necessary to prevent systems-wide organ pathology and reduce AD hallmark pathologies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":304047,"datarank":0.10879168325121917,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.004819606167227363,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.004819606167227363,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"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":996464,"name":"Jessica M. Judd","orcid":"0000-0001-9993-6391","position":1,"is_corresponding":false},{"id":996877,"name":"Annika Decker","orcid":null,"position":2,"is_corresponding":false},{"id":853278,"name":"Wendy Winslow","orcid":"0000-0001-9641-4010","position":3,"is_corresponding":false},{"id":996878,"name":"Patrick Sarette","orcid":null,"position":4,"is_corresponding":false},{"id":996879,"name":"Oscar Villareal Espinosa","orcid":null,"position":5,"is_corresponding":false},{"id":996880,"name":"Jessica Sandler","orcid":null,"position":6,"is_corresponding":false},{"id":355424,"name":"Alina S. Bilal","orcid":"0000-0003-1287-447X","position":7,"is_corresponding":false},{"id":996465,"name":"Savannah Tallino","orcid":"0000-0003-3683-259X","position":8,"is_corresponding":false},{"id":671075,"name":"Ian M. McDonough","orcid":"0000-0003-0907-8931","position":9,"is_corresponding":false},{"id":854037,"name":"Joanna K. Winstone","orcid":null,"position":10,"is_corresponding":false},{"id":331053,"name":"Erik A. Blackwood","orcid":"0000-0003-0912-4133","position":11,"is_corresponding":false},{"id":331051,"name":"Christopher C. Glembotski","orcid":"0000-0002-1380-5073","position":12,"is_corresponding":false},{"id":838964,"name":"Timothy L. Karr","orcid":"0000-0002-4180-6583","position":13,"is_corresponding":false},{"id":853279,"name":"Ramón Velázquez","orcid":"0000-0002-7722-0533","position":14,"is_corresponding":false},{"id":996463,"name":"Nikhil Dave","orcid":"0000-0002-6477-0587","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:28.468841Z","pmid":null,"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":[]}