Low plasma total cholesterol in patients with Huntington's disease and first-degree relatives.

Recent studies indicate altered cholesterol homeostasis in Huntington's disease (HD) after it was found that cultured human and mice cells expressing mutant huntingtin show reduced mRNA of cholesterol biosynthetic enzymes. Plasma total cholesterol (TC) levels have been connected to degenerative disorders, but data for HD are lacking. We estimated plasma TC in three groups of HD related subjects: (a) patients with overt symptomatology, (b) subjects with expanded CAG repeat number in the Huntington gene before disease onset, and (c) siblings or descendants of HD patients, with normal CAG repeat number. Compared to TC levels of age-matched controls, all three groups had significantly lower plasma TC levels. The expected positive correlation of TC to age, present in the control group, was absent in the whole group or the three subgroups of the HD subjects. TC of the ApoE genotype subgroups showed small, non-significant differences. In the group of patients, TC levels were not related to severity of illness, duration of illness, and presence of depression or dementia in their symptomatology, while lower TC levels were found in patients with psychotic features. The results indicate altered cholesterol homeostasis in members of families with HD patients. Low TC levels have been connected to increased suicide risk in several studies, and high suicidal ideation has been reported in both HD gene carriers and non-carriers. Although low plasma TC levels do not necessarily imply alterations in brain cholesterol levels, a more detailed study of plasma lipids in HD patients and their first-degree relatives, as well as the search for genetic factors regarding cholesterol synthesis and disposition, are warranted.