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Existing diffusion MRI approaches are either local or depend on predefined parcellations, limiting their ability to capture distributed network disruption. We introduce a streamline-wise framework to map axonal degeneration and derive disease-specific fiber \u201cdegeneromes\u201d across Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). We analyzed diffusion microstructure imaging and T1-weighted MRI (3\u2009T Siemens Prisma, 2018\u20132024) in AD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200981), PD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009177), MSA (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200950), PSP (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200935), and healthy controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200926). The intraaxonal volume fraction, estimated via a Bayesian three-compartment model, was mapped along ~20,000 normative streamlines in MNI space using age- and sex-adjusted regression with FDR correction. Streamline-wise mapping revealed disease-specific degeneromes consistent with established pathoanatomical models: AD involved limbic and temporo-occipital pathways, PD showed commissural and posterior association involvement, MSA affected pontocerebellar and corticospinal tracts, and PSP involved the dentato-rubro-thalamic tract and superior cerebellar peduncle. These signatures supported group-level differentiation, and streamline-wise z-scores enabled intuitive single-patient visualization. Fiber degeneromes offer a connectome-informed biomarker with strong biological plausibility, discriminatory potential across neurodegenerative entities, and a clear route toward clinical single-patient reporting.\n                  <\/jats:p>","DOI":"10.1038\/s41531-026-01428-2","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:24:35Z","timestamp":1781112275000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The degenerome\u2014a novel streamline-wise approach for white matter integrity in neurodegeneration"],"prefix":"10.1038","volume":"12","author":[{"given":"Jonas A.","family":"Hosp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Reisert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Schr\u00f6ter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Kellner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hansj\u00f6rg","family":"Mast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Rijntjes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Hellwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Frings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Wiendl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst","family":"Urbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Rau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"1428_CR1","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1007\/s10072-013-1406-9","volume":"34","author":"HC Shi","year":"2013","unstructured":"Shi, H. 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N.S. is a member of Mitsubishi Tanabe Pharma\u2019s and STADA advisory board and has received speaker honoraria and travel support from AbbVie, STADApharm, Merz, Novartis, Zambon, and EISAI.E.K. is a shareholder of and received fees from VEObrain GmbH, Freiburg, Germany. H.M.: The author declares no competing financial or non-financial interests. M.Rij.: The author declares no competing financial or non-financial interests. S.H.: The author declares no competing financial or non-financial interests. L.F.: The author declares no competing financial or non-financial interests. H.W. receives honoraria for serving on scientific advisory boards for Alexion, Argenx, Biocryst, Bristol Myers Squibb, Cellerys, Galapagos, Janssen, Merck, Novartis, Sandoz-Hexal, and uniQure biopharma B.V. He has received speaker honoraria and travel support from Alexion, AOCN, AstraZeneca, Biogen, BGP Products Operations GmbH, Bristol Myers Squibb, CEMCAT, EPG Health\/Medthority, Genzyme, Kohlhammer, Merck, MS at the Limits, Neurodiem, NMSS, Novartis, Ology, Roche, Sanofi, Springer, Streamed up, TEVA, Uvet, and WebMD Global. He acts as a paid consultant for Alexion, Argenx, Argobio, Bristol Myers Squibb, Dianthus, EMD Serono, Fondazione Cariplo, Idorsia, Immunic, Immunovant, INmune Bio, Syneos Health, Janssen, LTS, Lundbeck, Merck, Muna Therapeutics, Myrobalan Therapeutics, Novartis, PSL Group, Red Nucleus, Roche, Samsung, Sangamo, Sanofi, Swiss Multiple Sclerosis Society, Teladochealth, Toleranzia, UCB, and Viatris. His research is funded by Alexion, Amicus Therapeutics Inc., Argenx, Biogen, CSL Behring, F. Hoffmann\u2013La Roche, Genzyme, Merck KGaA, Novartis, Roche, and UCB Biopharma. H.U. serves on the advisory boards of Biogen and Lilly, and has received speaker honoraria from Biogen, Eisai, mbits, Bayer, and GE. He is co-editor of Clinical Neuroradiology and was not involved in the journal\u2019s review of, or decisions related to, this manuscript. A.R.: The author declares no competing financial or non-financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"139"}}