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Accelerated aging has been found in neurodegenerative disorders like Alzheimer\u2019s disease (AD), but its validation against markers of neurodegeneration and AD is lacking. Here, imaging-derived measures from the UK Biobank dataset (N=22,661) were used to predict brain-age in 2,314 cognitively unimpaired (CU) individuals at higher risk of AD and mild cognitive impaired (MCI) patients from four independent cohorts with available biomarker data: ALFA+, ADNI, EPAD, and OASIS. Brain-age delta was associated with abnormal amyloid-\u03b2, more advanced stages (AT) of AD pathology and\n                    <jats:italic>APOE<\/jats:italic>\n                    -\u03b54 status. Brain-age delta was positively associated with plasma neurofilament light, a marker of neurodegeneration, and sex differences in the brain effects of this marker were found. These results validate brain-age delta as a non-invasive marker of biological brain aging in non-demented individuals with abnormal levels of biomarkers of AD and axonal injury.\n                  <\/jats:p>","DOI":"10.7554\/elife.81067","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T08:15:17Z","timestamp":1681200917000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.81067","source":"Crossref","is-referenced-by-count":66,"title":["Biological brain age prediction using machine learning on structural neuroimaging data: Multi-cohort validation against biomarkers of Alzheimer\u2019s disease and neurodegeneration stratified by sex"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1967-7025","authenticated-orcid":true,"given":"Irene","family":"Cumplido-Mayoral","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01nry9c15","id-type":"ROR","asserted-by":"publisher"}],"name":"Barcelona\u03b2eta Brain 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