One explanation for reduced levels of LXR ligands in the CSF of ALS patients is that, as neurons die in ALS, less of the neuron-specific endoplasmic reticulum enzyme CYP46A1 is available to metabolize cholesterol to 24S-HC, thereby accounting for its reduced concentration in the CSF. This evidence concerns the gene CYP46A1 and amyotrophic lateral sclerosis.