Quantitative neuropathological changes in presymptomatic Huntington's disease

Morphometric studies of the tail of the caudate nucleus, the site where the pathology is first seen, were performed on 16 brain specimens collected fr om individuals at risk for inheriting Huntington's disease (HD), Medical re cords and information obtained from immediate family members indicated that all had died without symptoms of HD. Six individuals had 37 or more CAG re peats and were designated HD gene carriers, whereas 10 were determined to b e non-carriers. Cell counts of the tail of the caudate nucleus revealed an increased density of oligodendrocytes among the presymptomatic HD gene carr iers (mean cells/field: carriers = 40.0, noncarrier = 21.3; age, sex, repea ted measure adjusted F[126] 11.7, p = 0.0008). No statistically significant differences were found between HD carriers and noncarriers in the density of neurons (carriers = 16.9, noncarriers = 15.5), astrocytes (carriers = 27 .8, noncarriers = 21.3) or microglial cells (carriers = 7.9, noncarriers = 5.6). Ubiquitin immunostaining performed in 3 gene carriers revealed intran uclear inclusions in all 3 cases, including 1, with 37 repeats, who died 3 decades before the expected age for onset of the clinical syndrome. Normal densities of other cell types and careful macroscopic examination suggest t hat the increase in oligodendroglial density is not a consequence of atroph y and may instead reflect a developmental effect of the HD gene.