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Updated: Apr 30, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
Cortical interneuron loss and symptom heterogeneity in Huntington disease
Eric H Kim1, Doris C V Thu, Lynette J Tippett
1Department of Anatomy with Radiology, University of Auckland, Auckland, New Zealand; Centre for Brain Research, University of Auckland, Auckland, New Zealand.
Objective:
The cellular basis of variable symptoms in Huntington disease (HD) is unclear. One important possibility is that degeneration of the interneurons in the cerebral cortex, which play a critical role in modulating cortical output to the basal ganglia, might play a significant role in the development of variable symptomatology in HD. This study aimed to examine whether symptom variability in HD is specifically associated with variable degeneration of cortical interneurons.
Methods:
We undertook a double-blind study using stereological cell counting methods to quantify the 3 major types of γ-aminobutyric acidergic interneurons (calbindin-D28k, calretinin, parvalbumin) in 13 HD cases of variable motor/mood symptomatology and 15 matched control cases in the primary motor and anterior cingulate cortices.
Results:
In the primary motor cortex, there was a significant loss (57% reduction) of only calbindin interneurons (p=0.022) in HD cases dominated by motor symptoms, but no significant interneuron loss in cases with a dominant mood phenotype. In contrast, the anterior cingulate cortex showed a major significant loss in all 3 interneuron populations, with 71% loss of calbindin (p=0.001), 60% loss of calretinin (p=0.001), and 80% loss of parvalbumin interneurons (p=0.005) in HD cases with major mood disorder, and no interneuron loss was observed in cases with major motor dysfunction.
Interpretation:
These findings suggest that region-specific degeneration of cortical interneurons is a key component in understanding the neural basis of symptom heterogeneity in HD.
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