Accelerating Biomedical Discoveries in Aging and Neurodegeneration Through Transformative Neuropathology

• DOI: 10.20944/preprints202503.0628.v1
• Publication Date: 2025-03-13T00:38:17Z
• Authors: Melissa E. Murray; Colin Smith; Vilas Menon; C. Dirk Keen; Ed S. Lein; Michael Hawrylycz; Adriano Aguzzi; Brett Benedetti; Katja Brose; Kelsey Caetano-An...; Maria Inmaculada ...; John F. Crary; Phillip L. De Jager; Arline Faustin; Margaret E. Flanagan; Ozgun Gokce; Seth G.N. Grant; Lea T. Grinberg; David A. Gutman; Elizabeth M.C. Hi...; Zhi Huang; David J Irwin; David T. Jones; Alifiya Kapasi; Celeste M Karch; Walter A. Kukull; Tammaryn Lashley; Edward B. Lee; Thomas Lehner; Laura Parkkinen; Maria Pedersen; Dominique L. Prit...; Matthew H. Rutledge; Julie A. Schneider; William W. Seeley; Claire E Shepherd; Tara L. Spires-Jones; Judith A. Steen; Margaret Sutherland; Sanja Vickovic; Bin Zhang; David J. Stewart; Michael J. Keiser; Jacob W. Vogel; Brittany N Dugger; Hemali Phatnani

Transformative neuropathology is redefining human brain research by integrating foundational descriptive pathology with advanced methodologies to drive discoveries that inform diagnostics, therapeutics, and disease prevention. These approaches, spanning multi-omics studies and machine learning applications, enable the identification of biomarkers, therapeutic targets, and complex disease patterns through comprehensive analyses of postmortem human brain tissue. Yet critical challenges, including sustainability of brain banks, expanding donor participation, strengthening training pipelines, enabling rapid autopsies, and supporting collaborative platforms. Innovations in digital pathology, tissue quality enhancement, harmonized data standards, and machine learning integration offer groundbreaking opportunities to accelerate research in aging and neurodegeneration. Lessons from neuroimaging, regarding progress in establishing common data frameworks and multi-site collaborations, offer a valuable roadmap for streamlining innovations. In this Perspective, we outline actionable solutions to leverage existing resources, envision future opportunities, and advance collaboration to drive translational discoveries and safeguard the sustainability of brain banks underpinning transformative neuropathology.