Cholesterol is sequestered in the brains of mice with Niemann-Pick Type C disease but turnover is increased

In Niemann-Pick Type C (NPC) disease, the concentration of cholesterol incr eases with age in every tissue except the brain. This study investigates wh ether accumulation of cholesterol might also occur within the cells of the central nervous system (CNS), but be obscured by the simultaneous loss of s terol from myelin as neurodegeneration proceeds. At birth, when there is li ttle myelin in the CNS, the concentration of cholesterol is significantly e levated in every region of the brain in the homozygous NPC mouse. At 7 wk o f age, myelination is nearly complete. In the NPC mouse, however,there is s triking neurodegeneration and a reduction in both myelin protein and myelin cholesterol. Furthermore, net loss of cholesterol from the CNS is much hig her in the NPC mouse than in the control animal (2.23 versus 1.37 mg/day pe r kg) so that the concentration of sterol in most regions of the brain is r educed. This neurodegeneration and loss of myelin cholesterol is not preven ted by deletion of either the low-density lipoprotein receptor or apolipopr otein E in the NPC animal. Thus, the cholesterol sequestration seen in ever y organ in NPC disease also occurs in cells of the CNS and may be etiologic ally related to the neurodegeneration.