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This study employs explainable machine learning models to detect dementia cases using blood gene expression, single nucleotide polymorphisms (SNPs), and clinical data from Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI). Analyzing 623 ADNI participants, we found that the Support Vector Machine classifier with Mutual Information (MI) feature selection, trained on all three data modalities, achieved exceptional performance (accuracy = 0.95, AUC = 0.94). When using gene expression and SNP data separately, we achieved very good performance (AUC = 0.65, AUC = 0.63, respectively). Using SHapley Additive exPlanations (SHAP), we identified significant features, potentially serving as AD biomarkers. Notably, genetic-based biomarkers linked to axon myelination and synaptic vesicle membrane formation could aid early AD detection. In summary, this genetic-based biomarker approach, integrating machine learning and SHAP, shows promise for precise AD diagnosis, biomarker discovery, and offers novel insights for understanding and treating the disease. This approach addresses the challenges of accurate AD diagnosis, which is crucial given the complexities associated with the disease and the need for non-invasive diagnostic methods.<\/jats:p>","DOI":"10.1038\/s41598-024-56489-1","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T23:01:46Z","timestamp":1710284506000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Predicting early Alzheimer\u2019s with blood biomarkers and clinical features"],"prefix":"10.1038","volume":"14","author":[{"given":"Muaath Ebrahim","family":"AlMansoori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherlyn","family":"Jemimah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferial","family":"Abuhantash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aamna","family":"AlShehhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"56489_CR1","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1586\/14737159.2015.1002469","volume":"15","author":"C Reitz","year":"2015","unstructured":"Reitz, C. 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