Tangle-bearing neurons contain more free cholesterol than adjacent tangle-free neurons

Neurofibrillary tangles are seen both in senile dementia of Alzheimer's disease and in juvenile dementia of Niemann-Pick type C disease. Apolipoprotein E is a main cholesterol transport molecule in brain. In Alzheimer's disease, possession of the apolipoprotein E epsilon4 allele is associated with an earlier onset in tangle formation and an increased tangle load. Niemann-Pick type C disease is a disorder with elevated intracellular levels of free cholesterol due to a genetic deficit in its transport. The link between tangle formation and cholesterol metabolism in both diseases suggests that alterations of intracellular free cholesterol levels could influence tangle formation. Using semiquantitative fluorescence microscopy with the free cholesterol probe filipin and analysing 939 neurons, we observed that mean levels of free cholesterol in tangle-bearing neurons were higher than those of adjacent tangle-free neurons.