The major route for cholesterol metabolism in the CNS is conversion to 24S-HC via the neuron-specific enzyme CYP46A1 (32, 33), accounting for approximately two-thirds of cholesterol metabolism in brain, and elevated levels of total 24S-HC have been found in CSF of patients with some neurodegenerative diseases, e.g., Alzheimer’s disease (AD) (34, 35). The gene discussed is CYP46A1; the disease is early-onset autosomal dominant Alzheimer disease.