{"doi":"10.1126/sciadv.adu2937","title":"Gut-brain nexus: Mapping multimodal links to neurodegeneration at biobank scale","abstract":"Alzheimer's disease (AD) and Parkinson's disease (PD) are influenced by genetic and environmental factors. We conducted a biobank-scale study to (i) identify endocrine, nutritional, metabolic, and digestive disorders with potential causal or temporal associations with AD/PD risk before diagnosis; (ii) assess plasma biomarkers' specificity for AD/PD in the context of co-occurring gut related traits and disorders; and (iii) integrate multimodal datasets to enhance AD/PD prediction. Our findings show that several disorders were associated with increased AD/PD risk before diagnosis, with variation in the strength and timing of associations across conditions. Polygenic risk scores reveal lower genetic predisposition for AD/PD in individuals with co-occurring disorders. Moreover, the proteomic profile of AD/PD cases was influenced by comorbid gut-brain axis disorders. Last, our multimodal prediction models outperform single-modality paradigms in disease classification. This endeavor illuminates the interplay between factors involved in the gut-brain axis and the development of AD/PD, opening avenues for therapeutic targeting and early diagnosis.","journal":"Science Advances","year":2025,"id":521951,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1324941,"name":"Samantha Hong","orcid":"0009-0001-8968-6461","position":1,"is_corresponding":false},{"id":912146,"name":"Paul Suhwan Lee","orcid":"0000-0003-2658-4641","position":2,"is_corresponding":false},{"id":269472,"name":"Spencer Grant","orcid":null,"position":3,"is_corresponding":false},{"id":882320,"name":"Marzieh Khani","orcid":"0000-0003-0649-6644","position":4,"is_corresponding":false},{"id":806583,"name":"Anant Dadu","orcid":"0000-0002-6383-629X","position":5,"is_corresponding":false},{"id":279269,"name":"Artur Francisco Schumacher Schuh","orcid":"0000-0002-8722-0908","position":6,"is_corresponding":false},{"id":271540,"name":"Mary B. 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