A synthesis-based mapping of the landscape of neurodegenerative diseases

• A comprehensive map of 29 neurodegenerative diseases in human brain regions has been created • Frontal lobes emerge as critical regions with high prevalence of neurodegenerative diseases • Protein-based disease clustering allows visualization of the regional location of disease categories • The disease-function matrix identifies “hotspots” of cognitive functions susceptible to impairment • A linear relationship emerges between brain disease coverage and brain function impairment Neurodegenerative diseases (NDDs) exhibit heterogeneous patterns of anatomical involvement and cognitive impairment, yet a unified, brain-wide comparison across disorders is lacking. In this study, we synthesized published neuroimaging and neuropathological findings to construct a standardized, atlas-based mapping of 29 NDDs. Rather than analyzing primary MRI or PET datasets, we systematically extracted anatomical localization data from the literature and harmonized all reported regions using the 38-region Yale Brain Atlas. For each disease, we quantified affected regions, identified shared neuroanatomical signatures, and linked these patterns to 18 key cognitive and behavioral functions. Using this integrated dataset, we generated spatial heat maps, disease-region matrices, and a comprehensive disease-function matrix that captured the extent of functional disruption. Principal component and clustering analyses showed that neurodegenerative diseases form coherent groupings based on shared functional impact profiles, revealing robust latent structure in how anatomical degeneration translates into cognitive impairment. Finally, an interactive companion website has been developed to visualize disease-specific and cross-disease anatomical patterns. This synthesis-based mapping approach provides a unified landscape of neurodegeneration across molecular, anatomical, and functional dimensions, offering a transparent and accessible resource for understanding how diverse NDDs converge and diverge across the human brain.