Polyclonal Cholesterol 24-Hydroxylase C-terminal  Antiserum 

Cholesterol 24-hydroxylase (CYP46) is located exclusively in the brain and represents a new cytochrome P450 subfamily.  This enzyme is located in the endoplasmic reticulum of neurons and converts cholesterol to 24S-hydroxycholesterol, a polar metabolite capable of crossing the blood brain barrier and entering the circulation.  This movement of cholesterol metabolites across the blood brain barrier is important in maintaining cholesterol homeostasis in the brain as it has been shown that the rate of oxidation of cholesterol to 24S-hydroxycholesterol is similar to the rate of cholesterol synthesis in the brain.

Evidence is accumulating that indicates there is a link between cholesterol metabolism in the brain and susceptibility to Alzheimer’s disease (AD).  Studies have shown that brains of advanced AD patients contain less 24S-hydroxycholesterol than normal aged controls.  When the amounts and distribution of CYP46 levels were measured in autopsied brain, there was a reduction of CYP46 levels in the neurons of the frontal cortex of AD patients compared to controls.  Surprisingly, CYP46 activity was detected in the glial cells of the AD patients, but not the controls.  Since cholesterol levels appear to affect the deposition of amyloid β-protein (Aβ), reduced neuronal levels of CYP46 may lead to reduced cholesterol levels, which in turn promote the formation of aggregated Aβ.

A goat antiserum to a synthetic peptide that corresponds to amino acids 254-270 of the C-terminus of the human cholesterol 24-hydroxylase protein is currently available. This antiserum has been shown to be immunoreactive with the unconjugated immunizing peptide by ELISA and recognizes the ~ 58 kD CYP46 protein in western blotted brain samples. This antibody should be a valuable tool for scientists working to understand the role of CYP46 in Alzheimer’s and other neurological diseases.

An immunizing peptide (Cat no. HSP043C) is available which can be used to neutralize immunoreactivity.

Manufacturing Reference:

Lund, E.G., et al.  Proc. Natl. Acad. Sci. USA 96:7238-7243, 1999.