6. Huntington's Disease Pathology 🧠: USMLE Step 1

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Huntington's Disease Pathology
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Huntington's Disease (HD) is an inherited neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. It results from a genetic mutation in the HTT gene, which leads to abnormal expansion of a CAG repeat, producing a mutant form of the protein huntingtin. This malformed protein accumulates in the brain, causing toxicity and cellular dysfunction.

Key Pathological Features:
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Neuronal Degeneration: The most prominent damage occurs in the striatum, part of the basal ganglia involved in movement control, but as the disease progresses, it affects other areas of the brain, including the cortex.

Inclusion Bodies: Similar to other neurodegenerative disorders, HD features the presence of inclusion bodies within neurons, which are aggregates of the mutant huntingtin protein. These aggregates interfere with various cellular processes and contribute to cell death.

Neurochemical Changes: There is a significant reduction in the levels of several neurotransmitters, including GABA, acetylcholine, and glutamate, which disrupts normal neuronal communication and contributes to symptoms of the disease.

Neuroinflammation: Increased inflammation within the brain, particularly in affected areas, exacerbates neuronal damage. Microglial activation is a common feature, contributing further to the degenerative process.

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