Pyramidal cell loss in motor cortices in Huntington's disease

Patterns of huntingtin protein aggregation and cortical neuronal loss suggest early involvement of corticostriatal pathways in Huntington's disease. However, theories of pathogenesis of chorea rely on the motor cortices being intact. The motor cortices have not previously been studied at a cellular level in Huntington's disease. We analyzed the neuronal number in the caudate, putamen, and three motor cortical areas in five cases of Huntington's disease and five controls. For each motor cortical region the total neuronal number, number of interneurons, and number of SMI32 immunopositive pyramidal neurons were quantified using previously published techniques and any relationship between cell loss and severity or duration of chorea was examined. The results showed a loss of long projecting SMI32 immunopositive pyramidal neurons in the primary motor cortex with associated morphological changes and suggest a loss of short projecting pyramidal neurons in the premotor cortex. Degeneration in the primary motor cortex correlated with subcortical degeneration. These findings indicate pyramidal cell involvement in Huntington's disease and implicate the degeneration of corticostriatal pathways in the production of chorea.