ArticleNPJ Parkinson's disease2026
The degenerome-a novel streamline-wise approach for white matter integrity in neurodegeneration.
Article in NPJ Parkinson's disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Neurodegenerative diseases impair both gray matter and long-range white-matter pathways. 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 "degeneromes" across Alzheimer's disease (AD), Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). We analyzed diffusion microstructure imaging and T1-weighted MRI (3 T Siemens Prisma, 2018-2024) in AD (n = 81), PD (n = 177), MSA (n = 50), PSP (n = 35), and healthy controls (n = 26). 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.
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