J. Lipid Res.
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A more recent version of this article appeared on January 1, 2004

Papers In Press, published online ahead of print October 1, 2003
J. Lipid Res., doi:10.1194/jlr.M300320-JLR200
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Submitted on July 22, 2003
Revised on September 18, 2003
Accepted on September 25, 2003

Changes in the levels of cerebral and extracerebral sterols in the brain of patients with Alzheimer's disease

Maura Heverin, Nenad Bogdanovic, Dieter Lutjohann, Thomas Bayer, Irina Pikuleva, Lionel Bretillon, Ulf Diczfalusy, Bengt Winblad, and Ingemar Björkhem

Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge University Hospital, Stockholm S14186

Corresponding Author: ingemar.bjorkhem{at}hs.se

24S-hydroxycholesterol is a side-chain oxidised oxysterol formed in the brain that is continuously crossing the blood-brain barrier to reach the circulation. There may be an opposite flux of 27-hydroxycholesterol, which is formed to a lower extent in the brain than in most other organs. Here we measured cholesterol, lathosterol, 24S-and 27-hydroxycholesterol and plant sterols in 4 different brain areas of deceased Alzheimer’s disease (AD) patients and controls. 24S-Hydroxycholesterol was decreased and 27-hydroxycholesterol increased in all the brain samples from the AD patients. The difference was statistically significant in 4 of the 8 comparisons. The ratio between 27-hydroxycholesterol and 24S-hydroxycholesterol was significantly increased in all brain areas of the AD-patients and also in the brains of aged mice expressing the Swedish Alzheimer mutation APP751. Cholesterol 24S-hydroxylase and 27-hydroxylase protein was not significantly different between AD-patients and controls. A high correlation was observed between the levels of 24S-hydroxycholesterol and lathosterol in the frontal cortex of the AD-patients but not in the controls. Most probably the high levels of 27-hydroxycholesterol are due to increased influx of this steroid over the blood-brain barrier and the lower levels of 24S-hydroxycholesterol to decreased production. The high correlation between lathosterol and 24-hydroxycholesterol is consistent with a close coupling between synthesis and metabolism of cholesterol in the frontal cortex of the AD brain.


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