UNDERSTANDING NEURODEGENERATIVE DISEASE PATHOLOGY: A GUIDE FOR GENERAL NEUROLOGISTS

Neurodegeneration involves the progressive dysfunction or loss of selectively vulnerable neurons in the brain and spinal cord. Despite significant advancements in fluid and imaging biomarkers, the definitive diagnosis of most neurodegenerative diseases still depends on neuropathological examination. Careful clinicopathological correlation has been instrumental in shaping clinical diagnostic criteria, enhancing our understanding of disease progression, and uncovering conditions with substantial public health relevance, such as variant Creutzfeldt-Jakob disease, iatrogenic amyloid-β deposition, and chronic traumatic encephalopathy. Neuropathological analysis can also reveal previously undetected genetic conditions with potential implications for family members. Additionally, detailed postmortem tissue examination plays a vital role in research aimed at uncovering molecular mechanisms of neurodegeneration and developing or validating biomarkers. This review highlights the hallmark pathological features of neurodegenerative diseases commonly encountered in general neurology, including Alzheimer’s disease and Parkinson’s disease; rarer but recognized disorders like progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy; as well as emerging entities such as chronic traumatic encephalopathy and age-related tau astrogliopathy.