Neurodegenerative disorders are characterized by the progressive loss of specific neuronal populations, contrasting with static neuronal loss due to metabolic or toxic disorders. These disorders can be classified based on clinical features, anatomical distribution, or molecular abnormalities. The most common types include amyloidoses, tauopathies, α-synucleinopathies, and TDP-43 proteinopathies, all of which involve abnormal protein conformations. Experimental evidence suggests that these abnormal protein conformers may spread from cell to cell along anatomically connected pathways, explaining specific anatomical patterns observed at autopsy. Neuropathological evaluation at autopsy is the current gold standard for diagnosis, though diagnostic biomarkers are still lacking. The review details the human pathology of select neurodegenerative disorders, focusing on their main protein aggregates, and discusses the stereotypical progression of many disorders, as described by staging schemes. The article also highlights the importance of studying disease heterogeneity at autopsy to understand discrepancies between clinical and pathological diagnoses, which is crucial for developing biomarkers and monitoring disease progression.Neurodegenerative disorders are characterized by the progressive loss of specific neuronal populations, contrasting with static neuronal loss due to metabolic or toxic disorders. These disorders can be classified based on clinical features, anatomical distribution, or molecular abnormalities. The most common types include amyloidoses, tauopathies, α-synucleinopathies, and TDP-43 proteinopathies, all of which involve abnormal protein conformations. Experimental evidence suggests that these abnormal protein conformers may spread from cell to cell along anatomically connected pathways, explaining specific anatomical patterns observed at autopsy. Neuropathological evaluation at autopsy is the current gold standard for diagnosis, though diagnostic biomarkers are still lacking. The review details the human pathology of select neurodegenerative disorders, focusing on their main protein aggregates, and discusses the stereotypical progression of many disorders, as described by staging schemes. The article also highlights the importance of studying disease heterogeneity at autopsy to understand discrepancies between clinical and pathological diagnoses, which is crucial for developing biomarkers and monitoring disease progression.