Accelerating biomedical discoveries in brain health through transformative neuropathology of aging and neurodegeneration.
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Murray ME, Smith C, Menon V, Keene CD, Lein E, Hawrylycz M, Aguzzi A, Benedetti B, Brose K, Caetano-Anolles K, Sillero MIC, Crary JF, De Jager PL, Faustin A, Flanagan ME, Gokce O, Grant SGN, Grinberg LT, Gutman DA, Hillman EMC, Huang Z, Irwin DJ, Jones DT, Kapasi A, Karch CM, Kukull WT, Lashley T, Lee EB, Lehner T, Parkkinen L, Pedersen M, Pritchett D, Rutledge MH, Schneider JA, Seeley WW, Shepherd CE, Spires-Jones TL, Steen JA, Sutherland M, Vickovic S, Zhang B, Stewart DJ, Keiser MJ, Vogel JW, Dugger BN, Phatnani H
Neuron 113 (22) 3703-3721 [2025-11-19; online 2025-07-18]
Transformative neuropathology is redefining human brain research by integrating foundational descriptive pathology with advanced methodologies. These approaches, spanning multi-omics studies and machine learning applications, will drive discovery for the identification of biomarkers, therapeutic targets, and complex disease patterns through comprehensive analyses of postmortem human brain tissue. Yet critical challenges remain, including the sustainability of brain banks, expanding donor participation, strengthening training pipelines, enabling rapid autopsies, supporting collaborative platforms, and integrating data across modalities. Innovations in digital pathology, tissue quality enhancement, harmonization of data standards, and machine learning integration offer opportunities to accelerate tissue-level "pathomics" research in brain health through cross-disciplinary collaborations. Lessons from neuroimaging, particularly in establishing common data frameworks and multi-site collaborations, offer a valuable roadmap for streamlining innovations. In this perspective, we outline actionable solutions for leveraging existing resources and strengthening collaboration -where we envision future opportunities to drive translational discoveries stemming from transformative neuropathology.
PubMed 40683248
DOI 10.1016/j.neuron.2025.06.014
Crossref 10.1016/j.neuron.2025.06.014
mid: NIHMS2092052
pmc: PMC12313173
pii: S0896-6273(25)00472-6