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Here, we introduce BrainAgeMap, an interpretable deep learning framework that generates fine-grained, voxel-wise maps of brain-predicted age difference (brain-PAD) from T1-weighted magnetic resonance imaging scans. We provide converging lines of evidence for the framework\u2019s clinical, prognostic, and neurobiological utility. Disorder-specific topographies of accelerated aging were identified in Alzheimer\u2019s disease (AD), frontotemporal dementia, and schizophrenia. Longitudinal analysis of the hippocampus revealed accelerated aging in individuals with progressive versus stable mild cognitive impairment (MCI), demonstrating prognostic value. Regional brain-PAD in the temporal lobe correlated strongly with\n                  <jats:italic>in vivo<\/jats:italic>\n                  tau pathology measured by positron emission tomography in AD, linking the maps to underlying molecular pathology. Furthermore, regional brain aging in MCI and AD was linked to individual differences in episodic memory function. BrainAgeMap provides a robust tool to delineate disease-specific pathways of neurodegeneration, offering new opportunities for early diagnosis, patient stratification, and monitoring therapeutic interventions.\n                <\/jats:p>","DOI":"10.1101\/2025.11.12.25339989","type":"posted-content","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T21:10:16Z","timestamp":1763154616000},"source":"Crossref","is-referenced-by-count":0,"title":["Regional brain aging patterns reveal disease-specific pathways of neurodegeneration"],"prefix":"10.64898","author":[{"given":"P\u00e1l","family":"Vakli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9la","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2115-9534","authenticated-orcid":false,"given":"Attila","family":"Keresztes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Hermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI)","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1908-5588","authenticated-orcid":false,"given":"James H.","family":"Cole","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zolt\u00e1n","family":"Vidny\u00e1nszky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025111701000645000_2025.11.12.25339989v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2017.10.001"},{"key":"2025111701000645000_2025.11.12.25339989v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0098-1"},{"key":"2025111701000645000_2025.11.12.25339989v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s43588-024-00659-8"},{"key":"2025111701000645000_2025.11.12.25339989v1.4","doi-asserted-by":"crossref","unstructured":"Papouli, A. & Cole, J. 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