{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T21:59:10Z","timestamp":1781819950479,"version":"3.54.5"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UE through Balearic Island Govern","award":["PROSALUT 2023-20"],"award-info":[{"award-number":["PROSALUT 2023-20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Introduction: Alzheimer\u2019s disease (AD), and more specifically late-onset Alzheimer\u2019s disease (LOAD), represents a considerable challenge in terms of early and timely diagnosis and treatment. Early diagnosis is crucial to improve the efficacy of the therapies and patients\u2019 quality of life. The current challenge is to accurately identify at-risk individuals before the manifestations of the first symptoms of AD. Methods and results: Here, we present an improved model for LOAD risk prediction, which applies the k-nearest neighbors (KNN) algorithm. We have achieved a sensitivity of 0.80 and an area under the curve (AUC) of 0.71, which represents a high performance especially when compared to an AUC of 0.66 reported previously in 2019 using a KNN model. Discussion: The application of a mathematical model that combines genetic and clinical covariates showed a good prediction of the AD\/LOAD risk, with the higher weight being the polygenic genetic risk, APOE haplotype, and age. Compared to previous studies, our model integrates and correlates genetic prediction together with phenotypic information by fine-tuning the parameters of the model in order to achieve the best performance. This algorithm can be used in the general population and does not require the manifestation of any symptoms for its effective application. Thus, we present here an advanced model for risk prediction of LOAD.<\/jats:p>","DOI":"10.3390\/genes16040377","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T04:36:48Z","timestamp":1743136608000},"page":"377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of a k-Nearest Neighbors Model for the Prediction of Late-Onset Alzheimer\u2019s Risk by Combining Polygenic Risk Scores and Phenotypic Variables"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9303-0515","authenticated-orcid":false,"given":"Sandra","family":"Ferreiro L\u00f3pez","sequence":"first","affiliation":[{"name":"ADNTRO Genetics, Carretera Betlem, s\/n, Colonia de Sant Pere, 07579 Arta, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-0231","authenticated-orcid":false,"given":"Rosana","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Center of Applied Ecology and Sustainability (CAPES), Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Blom-Dahl","sequence":"additional","affiliation":[{"name":"ADNTRO Genetics, Carretera Betlem, s\/n, Colonia de Sant Pere, 07579 Arta, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Alonso-Bern\u00e1ldez","sequence":"additional","affiliation":[{"name":"ADNTRO Genetics, Carretera Betlem, s\/n, Colonia de Sant Pere, 07579 Arta, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad\u00e1n","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"ADNTRO Genetics, Carretera Betlem, s\/n, Colonia de Sant Pere, 07579 Arta, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"P\u00e9rez-Solero","sequence":"additional","affiliation":[{"name":"ADNTRO Genetics, Carretera Betlem, s\/n, Colonia de Sant Pere, 07579 Arta, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5308-2316","authenticated-orcid":false,"given":"Jair","family":"Tenorio-Castano","sequence":"additional","affiliation":[{"name":"ADNTRO Genetics, Carretera Betlem, s\/n, Colonia de Sant Pere, 07579 Arta, Spain"},{"name":"INGEMM, Institute of Medical and Molecular Genetics, La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain"},{"name":"ITHACA, European Research Network, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"Network for Biomedical Research on Rare Diseases (CIBERER), Carlos III Health Institute (ISCIII), 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1002\/alz.13016","article-title":"2023 Alzheimer\u2019s Disease Facts and Figures","volume":"19","author":"Better","year":"2023","journal-title":"Alzheimers Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.nrl.2016.02.016","article-title":"Prevalence and Incidence of Alzheimer\u2019s Disease in Europe: A Meta-Analysis","volume":"32","author":"Niu","year":"2017","journal-title":"Neurolog\u00eda"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s Disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/B978-0-12-804766-8.00013-3","article-title":"Alzheimer\u2019s Disease","volume":"Volume 167","year":"2019","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"225","DOI":"10.14283\/jpad.2018.34","article-title":"Female Sex and Alzheimer\u2019s Risk: The Menopause Connection","volume":"5","author":"Scheyer","year":"2018","journal-title":"J. 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