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A Genetic Risk Factor for Alzheimer Disease

Arch Neurol. 2003;60:16-18.

	Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.

THIS ISSUE of the ARCHIVES presents an elegant study by Papassotiropoulos and colleagues,¹ demonstrating that a polymorphism in the gene coding for Cyp46 (also known as 24S-cholesterol hydroxylase) is a major risk factor for late-onset Alzheimer disease (LOAD). The Cyp46 enzyme is a member of the cytochrome P450 family of proteins and converts cholesterol to 24-hydroxycholesterol (24-OHC).² Cyp46 is expressed exclusively in the brain, where it regulates the elimination of excess cholesterol by adding a hydroxyl group to cholesterol, producing a product that is more soluble than cholesterol and able to be exported from the brain.^2-3 Thus, cholesterol exits the brain by conversion to 24 OHC, and the amount of 24-OHC exiting the brain is thought to equal the amount of cholesterol endogenously synthesized within the brain. Less Cyp46 presumably leads to more brain cholesterol.

A brief review of the biology of AD is helpful in understanding how Cyp46 might . . . [Full Text of this Article]

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