Accelerating biomedical discoveries in brain health through transformative neuropathology of aging and neurodegeneration

Melissa E Murray¹, Colin Smith², Vilas Menon³, C Dirk Keene⁴, Ed Lein⁵, Michael Hawrylycz⁶, Adriano Aguzzi⁷, Brett Benedetti⁸, Katja Brose⁸, Kelsey Caetano-Anolles⁹, Maria Inmaculada Cobos Sillero¹⁰, John F Crary¹¹, Philip L De Jager¹², Arline Faustin¹³, Margaret E Flanagan¹⁴, Ozgun Gokce¹⁵, Seth G N Grant², Lea T Grinberg¹⁶, David A Gutman¹⁷, Elizabeth M C Hillman¹⁸, Zhi Huang¹⁹, David J Irwin¹⁹, David T Jones²⁰, Alifiya Kapasi²¹, Celeste M Karch²², Walter T Kukull²³, Tammaryn Lashley²⁴, Edward B Lee¹⁹, Thomas Lehner²⁵, Laura Parkkinen²⁶, Maria Pedersen²⁵, Dominique Pritchett²⁷, Matthew H Rutledge²⁸, Julie A Schneider²¹, William W Seeley¹⁶, Claire E Shepherd²⁹, Tara L Spires-Jones², Judith A Steen³⁰, Margaret Sutherland⁸, Sanja Vickovic³¹, Bin Zhang³², David J Stewart³³, Michael J Keiser³⁴, Jacob W Vogel³⁵, Brittany N Dugger³⁶, Hemali Phatnani³⁷

Affiliations

¹ Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA; Department of Laboratory Medicine and Pathology, Mayo Clinic Jacksonville, Jacksonville, FL, USA. Electronic address: murray.melissa@mayo.edu.
² Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
³ Department of Neurology, Columbia University, New York, NY, USA; Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
⁴ Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.
⁵ Allen Institute for Brain Science, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
⁶ Allen Institute for Brain Science, Seattle, WA, USA.
⁷ Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
⁸ Chan Zuckerberg Initiative (CZI), Redwood City, CA, USA.
⁹ Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
¹⁰ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
¹¹ Department of Pathology, Nash Family Department of Neuroscience, Department of Artificial Intelligence & Human Health, Neuropathology Brain Bank & Research CoRE, Ronald M. Loeb Center for Alzheimer's Disease, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹² Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.
¹³ Department of Pathology, NYU Langone Health and NYU Grossman School of Medicine, New York, NY, USA.
¹⁴ Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health, San Antonio, San Antonio, TX, USA; Department of Pathology, University of Texas Health, San Antonio, San Antonio, TX, USA.
¹⁵ Department of Old Age Psychiatry and Cognitive Disorders, University Hospital Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
¹⁶ Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
¹⁷ Emory University School of Medicine, Atlanta, GA, USA.
¹⁸ Zuckerman Mind Brain Behavior Institute and Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY, USA.
¹⁹ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁰ Department of Neurology, Mayo Clinic, Rochester, MN, USA; Department of Radiology, Mayo Clinic, Rochester, MN, USA.
²¹ Rush University Medical Center, Rush Alzheimer's Disease Center, Chicago, IL, USA.
²² Department of Psychiatry, Knight Alzheimer Disease Research Center, Washington University in St. Louis, St. Louis, MO, USA.
²³ Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.
²⁴ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
²⁵ New York Genome Center, New York, NY, USA.
²⁶ Nuffield Department of Clinical Neurosciences, Oxford Parkinson's Disease Center, University of Oxford, Oxford, UK.
²⁷ Department of Biology, Howard University, Washington, DC, USA.
²⁸ Quantitative Health Sciences, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
²⁹ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; School of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia.
³⁰ Department of Neurology, Harvard Medical School, Boston, MA, USA; Neuroproteomics Laboratory, Kirby Center, Boston Children's Hospital, Boston, MA, USA.
³¹ New York Genome Center, New York, NY, USA; Department of Biomedical Engineering and Herbert Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA.
³² Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³³ Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
³⁴ Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
³⁵ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Department of Clinical Sciences, Malmö, SciLifeLab, Lund University, Lund, Sweden.
³⁶ Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA.
³⁷ Department of Neurology, Columbia University, New York, NY, USA; New York Genome Center, New York, NY, USA. Electronic address: hphatnani@nygenome.org.

PMID: 40683248
PMCID: PMC12313173 (available on 2026-07-15)
DOI: 10.1016/j.neuron.2025.06.014

Review

Accelerating biomedical discoveries in brain health through transformative neuropathology of aging and neurodegeneration

Melissa E Murray et al. Neuron. 2025.

. 2025 Jul 15:S0896-6273(25)00472-6.

doi: 10.1016/j.neuron.2025.06.014. Online ahead of print.

Authors

Affiliations

¹ Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA; Department of Laboratory Medicine and Pathology, Mayo Clinic Jacksonville, Jacksonville, FL, USA. Electronic address: murray.melissa@mayo.edu.
² Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
³ Department of Neurology, Columbia University, New York, NY, USA; Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
⁴ Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.
⁵ Allen Institute for Brain Science, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
⁶ Allen Institute for Brain Science, Seattle, WA, USA.
⁷ Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
⁸ Chan Zuckerberg Initiative (CZI), Redwood City, CA, USA.
⁹ Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
¹⁰ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
¹¹ Department of Pathology, Nash Family Department of Neuroscience, Department of Artificial Intelligence & Human Health, Neuropathology Brain Bank & Research CoRE, Ronald M. Loeb Center for Alzheimer's Disease, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹² Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.
¹³ Department of Pathology, NYU Langone Health and NYU Grossman School of Medicine, New York, NY, USA.
¹⁴ Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health, San Antonio, San Antonio, TX, USA; Department of Pathology, University of Texas Health, San Antonio, San Antonio, TX, USA.
¹⁵ Department of Old Age Psychiatry and Cognitive Disorders, University Hospital Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
¹⁶ Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
¹⁷ Emory University School of Medicine, Atlanta, GA, USA.
¹⁸ Zuckerman Mind Brain Behavior Institute and Departments of Biomedical Engineering and Radiology, Columbia University, New York, NY, USA.
¹⁹ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁰ Department of Neurology, Mayo Clinic, Rochester, MN, USA; Department of Radiology, Mayo Clinic, Rochester, MN, USA.
²¹ Rush University Medical Center, Rush Alzheimer's Disease Center, Chicago, IL, USA.
²² Department of Psychiatry, Knight Alzheimer Disease Research Center, Washington University in St. Louis, St. Louis, MO, USA.
²³ Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.
²⁴ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
²⁵ New York Genome Center, New York, NY, USA.
²⁶ Nuffield Department of Clinical Neurosciences, Oxford Parkinson's Disease Center, University of Oxford, Oxford, UK.
²⁷ Department of Biology, Howard University, Washington, DC, USA.
²⁸ Quantitative Health Sciences, Mayo Clinic Jacksonville, Jacksonville, FL, USA.
²⁹ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; School of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia.
³⁰ Department of Neurology, Harvard Medical School, Boston, MA, USA; Neuroproteomics Laboratory, Kirby Center, Boston Children's Hospital, Boston, MA, USA.
³¹ New York Genome Center, New York, NY, USA; Department of Biomedical Engineering and Herbert Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA.
³² Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³³ Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
³⁴ Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
³⁵ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Department of Clinical Sciences, Malmö, SciLifeLab, Lund University, Lund, Sweden.
³⁶ Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA.
³⁷ Department of Neurology, Columbia University, New York, NY, USA; New York Genome Center, New York, NY, USA. Electronic address: hphatnani@nygenome.org.

PMID: 40683248
PMCID: PMC12313173 (available on 2026-07-15)
DOI: 10.1016/j.neuron.2025.06.014

Abstract

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.

Keywords: biomarkers; digital pathology; machine learning; neuropathology; pathomics; spatial biology.

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Conflict of interest statement

Declaration of interests C.M.K. is a consultant for Eisai, Ltd. W.W.S. serves on the scientific advisory board for Lyterian Therapeutics. L.P. is funded by the Oxford GSK Institute of Molecular and Computational Medicine. D.J.I. holds unpaid professional affiliations with the Scientific Advisory Boards of the Lewy Body Dementia Association (LBDA) and the Association for Frontotemporal Degeneration (AFTD). His institution receives clinical trial funding from Denali, Prevail, Passage Bio, CervoMed, and Transposon. E.B.L. has received consulting fees from Eli Lilly and Wavebreak Therapeutics. T.L.S.-J. declares no conflicts directly related to this manuscript but has received payments for consulting, scientific talks, or collaborative research over the past 10 years from AbbVie, Sanofi, Merck, Scottish Brain Sciences, Jay Therapeutics, Cognition Therapeutics, Ono, and Eisai. She also serves as a charity trustee for the British Neuroscience Association and the Guarantors of Brain and as a scientific advisor to several charities and non-profit organizations. W.T.K. is supported by U24AG072122.

References

1. Danner B, Gonzalez AD, Corbett WC, Alhneif M, Etemadmoghadam S, Parker-Garza J, and Flanagan ME (2024). Brain banking in the United States and Europe: Importance, challenges, and future trends. Journal of Neuropathology & Experimental Neurology 83, 219–229. 10.1093/jnen/nlae014. - DOI - PMC - PubMed
1. Bell JE, Alafuzoff I, Al-Sarraj S, Arzberger T, Bogdanovic N, Budka H, Dexter DT, Falkai P, Ferrer I, Gelpi E, et al. (2008). Management of a twenty-first century brain bank: experience in the BrainNet Europe consortium. Acta Neuropathol 115, 497–507. 10.1007/s00401-008-0360-8. - DOI - PubMed
1. Beach TG (2013). Alzheimer’s disease and the “Valley Of Death”: not enough guidance from human brain tissue? J Alzheimers Dis 33 Suppl 1, S219–233. 10.3233/JAD-2012-129020. - DOI - PubMed
1. Samarasekera N, Al-Shahi Salman R, Huitinga I, Klioueva N, McLean CA, Kretzschmar H, Smith C, and Ironside JW (2013). Brain banking for neurological disorders. Lancet Neurol 12, 1096–1105. 10.1016/S1474-4422(13)70202-3. - DOI - PubMed
1. Carlos AF, Poloni TE, Medici V, Chikhladze M, Guaita A, and Ceroni M (2019). From brain collections to modern brain banks: A historical perspective. Alzheimers Dement (N Y) 5, 52–60. 10.1016/j.trci.2018.12.002. - DOI - PMC - PubMed

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Accelerating biomedical discoveries in brain health through transformative neuropathology of aging and neurodegeneration

Affiliations

Accelerating biomedical discoveries in brain health through transformative neuropathology of aging and neurodegeneration

Authors

Affiliations

Abstract

Conflict of interest statement

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