| Title: |
Gut-brain nexus: Mapping multimodal links to neurodegeneration at biobank scale |
| Authors: |
Shafieinouri, Mohammad; Hong, Samantha; Lee, Paul Suhwan; Grant, Spencer M; Khani, Marzieh; Dadu, Anant; Schumacher Schuh, Artur F; Makarious, Mary B; Sandon, Rodrigo; Simmonds, Emily; Iwaki, Hirotaka; Hill, Gracelyn; Blauwendraat, Cornelis; Escott-Price, Valentina; Qi, Yue A; Noyce, Alastair J; Reyes-Palomares, Armando; Leonard, Hampton L; Tansey, Malu; Faghri, Faraz; Singleton, Andrew B; Nalls, Mike A; Levine, Kristin S; Bandres-Ciga, Sara |
| Publisher Information: |
American Association for the Advancement of Science |
| Publication Year: |
2025 |
| Collection: |
Cardiff University: ORCA (Online Research @ Cardiff) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://orca.cardiff.ac.uk/id/eprint/180998/1/10.1126_sciadv.adu2937.pdf; Shafieinouri, Mohammad, Hong, Samantha, Lee, Paul Suhwan, Grant, Spencer M, Khani, Marzieh, Dadu, Anant, Schumacher Schuh, Artur F, Makarious, Mary B, Sandon, Rodrigo, Simmonds, Emily, Iwaki, Hirotaka, Hill, Gracelyn, Blauwendraat, Cornelis, Escott-Price, Valentina https://orca.cardiff.ac.uk/view/cardiffauthors/A015705M.html orcid:0000-0003-1784-5483 orcid:0000-0003-1784-5483, Qi, Yue A, Noyce, Alastair J, Reyes-Palomares, Armando, Leonard, Hampton L, Tansey, Malu, Faghri, Faraz, Singleton, Andrew B, Nalls, Mike A, Levine, Kristin S and Bandres-Ciga, Sara 2025. Gut-brain nexus: Mapping multimodal links to neurodegeneration at biobank scale. Science Advances 11 (35) , eadu2937. 10.1126/sciadv.adu2937 https://doi.org/10.1126/sciadv.adu2937 file https://orca.cardiff.ac.uk/id/eprint/180998/1/10.1126_sciadv.adu2937.pdf |
| DOI: |
10.1126/sciadv.adu2937 |
| Availability: |
https://orca.cardiff.ac.uk/id/eprint/180998/; https://doi.org/10.1126/sciadv.adu2937; https://orca.cardiff.ac.uk/id/eprint/180998/1/10.1126_sciadv.adu2937.pdf |
| Rights: |
cc_by_nc_4_0 |
| Accession Number: |
edsbas.54D48D1F |
| Database: |
BASE |