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on February 5, 2004

Arteriosclerosis, Thrombosis, and Vascular Biology. 2004
Published online before print February 5, 2004, doi: 10.1161/01.ATV.0000120374.59826.1b
A more recent version of this article appeared on May 1, 2004
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Submitted on December 3, 2003
Accepted on January 22, 2004

Brain Cholesterol: Long Secret Life Behind a Barrier

Ingemar Björkhem * and Steve Meaney

From the Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.

* To whom correspondence should be addressed. E-mail: ingemar.bjorkhem{at}hs.se.

Abstract--Although an immense knowledge has accumulated concerning regulation of cholesterol homeostasis in the body, this does not include the brain, where details are just emerging. Approximately 25% of the total amount of the cholesterol present in humans is localized to this organ, most of it present in myelin. Almost all brain cholesterol is a product of local synthesis, with the blood-brain barrier efficiently protecting it from exchange with lipoprotein cholesterol in the circulation. Thus, there is a highly efficient apolipoprotein-dependent recycling of cholesterol in the brain, with minimal losses to the circulation. Under steady-state conditions, most of the de novo synthesis of cholesterol in the brain appears to be balanced by excretion of the cytochrome P-450-generated oxysterol 24S-hydroxycholesterol. This oxysterol is capable of escaping the recycling mechanism and traversing the blood-brain barrier. Cholesterol levels and cholesterol turnover are affected in neurodegenerating disorders, and the capacity for cholesterol transport and recycling in the brain seems to be of importance for the development of such diseases. The possibility has been discussed that administration of inhibitors of cholesterol synthesis may reduce the prevalence of Alzheimer disease. No firm conclusions can, however, be drawn from the studies presented thus far. In the present review, the most recent advances in our understanding of cholesterol turnover in the brain is discussed.
Key words: brain cholesterol • blood-brain barrier • cholesterol 24S-hydroxylase • Alzheimer disease • statins




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