Neurodegenerative diseases are characterized by the progressive loss of specific populations of neurons, distinct from static neuronal loss due to metabolic or toxic disorders. These diseases can be classified based on clinical features, anatomical distribution, or principal molecular abnormalities. The most common neurodegenerative disorders include amyloidoses, tauopathies, α-synucleinopathies, and TDP-43 proteinopathies. Abnormal protein conformations in these disorders are key histopathologic features. Experimental evidence suggests that abnormal proteins may spread between cells, contributing to specific anatomical patterns observed at autopsy. Neurodegenerative diseases share fundamental processes such as proteotoxic stress, oxidative stress, programmed cell death, and neuroinflammation. Protein abnormalities can precede clinical symptoms and multiple processes may coexist in an individual. Diagnostic biomarkers are limited, except in rare cases with known genetic mutations. In vivo biomarkers and molecular imaging are important research priorities. The most common neurodegenerative disorders are amyloidoses, tauopathies, α-synucleinopathies, and TDP-43 proteinopathies. Abnormal protein conformations in these disorders and their cellular and neuroanatomical distribution are essential for diagnosis. Examples include tau in neurofibrillary tangles or Pick bodies, α-synuclein in Lewy bodies, and TDP-43 in neuronal cytoplasmic and intranuclear inclusions. Protein accumulations in astrocytes and oligodendroglia also occur. These aggregates are composed of intrinsic neuronal proteins, unlike those in viral infections. Many form filaments with β-pleated sheets, and amyloid stains like Congo red and thioflavin S can detect many aggregates. Immunohistochemistry is preferred for studying neurodegenerative disorders due to better interlaboratory and inter-rater reliability. Staging schemes have been developed for Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, amyotrophic lateral sclerosis, frontotemporal lobar degeneration with TDP-43 pathology, and chronic traumatic encephalopathy. These schemes help describe the stereotypic progression of many neurodegenerative disorders. Amyloidoses are characterized by insoluble fibrous proteins with β-sheet-rich structures, often detected with specific dyes. Amyloid plaques have various morphologies and are found in the brain parenchyma or blood vessel walls. Amyloid plaques are heterogeneous and include dense cores, especially in primary cortices. Amyloid deposits are also found in other neurodegenerative disorders, such as prion diseases. Prion diseases involve the conversion of the normal prion protein (PrP^C) to the pathogenic form (PrP^Sc). These diseases are transmissible and classified as infectious. They include conditions like Gerstmann–Sträussler–Scheinker disease, Creutzfeldt–JakNeurodegenerative diseases are characterized by the progressive loss of specific populations of neurons, distinct from static neuronal loss due to metabolic or toxic disorders. These diseases can be classified based on clinical features, anatomical distribution, or principal molecular abnormalities. The most common neurodegenerative disorders include amyloidoses, tauopathies, α-synucleinopathies, and TDP-43 proteinopathies. Abnormal protein conformations in these disorders are key histopathologic features. Experimental evidence suggests that abnormal proteins may spread between cells, contributing to specific anatomical patterns observed at autopsy. Neurodegenerative diseases share fundamental processes such as proteotoxic stress, oxidative stress, programmed cell death, and neuroinflammation. Protein abnormalities can precede clinical symptoms and multiple processes may coexist in an individual. Diagnostic biomarkers are limited, except in rare cases with known genetic mutations. In vivo biomarkers and molecular imaging are important research priorities. The most common neurodegenerative disorders are amyloidoses, tauopathies, α-synucleinopathies, and TDP-43 proteinopathies. Abnormal protein conformations in these disorders and their cellular and neuroanatomical distribution are essential for diagnosis. Examples include tau in neurofibrillary tangles or Pick bodies, α-synuclein in Lewy bodies, and TDP-43 in neuronal cytoplasmic and intranuclear inclusions. Protein accumulations in astrocytes and oligodendroglia also occur. These aggregates are composed of intrinsic neuronal proteins, unlike those in viral infections. Many form filaments with β-pleated sheets, and amyloid stains like Congo red and thioflavin S can detect many aggregates. Immunohistochemistry is preferred for studying neurodegenerative disorders due to better interlaboratory and inter-rater reliability. Staging schemes have been developed for Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, amyotrophic lateral sclerosis, frontotemporal lobar degeneration with TDP-43 pathology, and chronic traumatic encephalopathy. These schemes help describe the stereotypic progression of many neurodegenerative disorders. Amyloidoses are characterized by insoluble fibrous proteins with β-sheet-rich structures, often detected with specific dyes. Amyloid plaques have various morphologies and are found in the brain parenchyma or blood vessel walls. Amyloid plaques are heterogeneous and include dense cores, especially in primary cortices. Amyloid deposits are also found in other neurodegenerative disorders, such as prion diseases. Prion diseases involve the conversion of the normal prion protein (PrP^C) to the pathogenic form (PrP^Sc). These diseases are transmissible and classified as infectious. They include conditions like Gerstmann–Sträussler–Scheinker disease, Creutzfeldt–Jak