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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.<\/jats:p>","DOI":"10.1126\/sciadv.adu2937","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T17:59:06Z","timestamp":1756317546000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Gut-brain nexus: Mapping multimodal links to neurodegeneration at biobank scale"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8562-1684","authenticated-orcid":true,"given":"Mohammad","family":"Shafieinouri","sequence":"first","affiliation":[{"name":"Center for Alzheimer\u2019s and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, 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