{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:50:34Z","timestamp":1790769034238,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,5,13]],"date-time":"2014-05-13T00:00:00Z","timestamp":1399939200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We undertook a double\u2010blind study using stereological cell counting methods to quantify the 3 major types of \u03b3\u2010aminobutyric acidergic interneurons (calbindin\u2010D28k, calretinin, parvalbumin) in 13 HD cases of variable motor\/mood symptomatology and 15 matched control cases in the primary motor and anterior cingulate cortices.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the primary motor cortex, there was a significant loss (57% reduction) of only calbindin interneurons (<jats:italic>p<\/jats:italic>\u2009=\u20090.022) 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 (<jats:italic>p<\/jats:italic>\u2009=\u20090.001), 60% loss of calretinin (<jats:italic>p<\/jats:italic>\u2009=\u20090.001), and 80% loss of parvalbumin interneurons (<jats:italic>p<\/jats:italic>\u2009=\u20090.005) in HD cases with major mood disorder, and no interneuron loss was observed in cases with major motor dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These findings suggest that region\u2010specific degeneration of cortical interneurons is a key component in understanding the neural basis of symptom heterogeneity in HD. Ann Neurol 2014;75:717\u2013727<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24162","type":"journal-article","created":{"date-parts":[[2014,4,26]],"date-time":"2014-04-26T09:34:52Z","timestamp":1398504892000},"page":"717-727","source":"Crossref","is-referenced-by-count":79,"title":["Cortical interneuron loss and symptom heterogeneity in Huntington disease"],"prefix":"10.1002","volume":"75","author":[{"given":"Eric H.","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Anatomy with Radiology University of Auckland Auckland New Zealand"},{"name":"Centre for Brain Research University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris C. 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