ABSTRACT

Objective

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder characterized by variable motor and behavioural symptoms attributed to major neuropathology of mainly the basal ganglia and cerebral cortex. The role of the cerebellum, a brain region involved in the coordination of movements, in HD neuropathology has been controversial. This study utilises post‐mortem human brain tissue to investigate whether Purkinje cell degeneration in the neocerebellum is present in HD, and how this relates to disease symptom profiles.

Methods

Unbiased stereological counting methods were used to quantify the total number of Purkinje cells in 15 HD cases and 8 neurologically normal control cases. Based on their predominant symptoms, the HD cases were categorised into two groups: “motor” or “mood”.

Results

The results demonstrated a significant 43% loss of Purkinje cells in HD cases with predominantly motor symptoms, and no cell loss in cases showing a major mood phenotype. There was no significant correlation between Purkinje cell loss and striatal neuropathological grade, post‐mortem delay, CAG repeat in the IT15 gene or age at death.

Interpretation

This study shows a compelling relationship between Purkinje cell loss in the HD neocerebellum and the HD motor symptom phenotype, which, together with our previous human brain studies on the same HD cases, provide novel perspectives interrelating and correlating the variable cerebellar, basal ganglia and neocortical neuropathology with the variability of motor/mood symptom profiles in the human HD brain.

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