Plasma levels of 24S-hydroxycholesterol in patients with neurological diseases Lionel Bretillon a,b ,A Ê ke Side Ân c , Lars-Olof Wahlund d , Dieter Lu È tjohann e , Lennart Minthon f , Milita Crisby c , Jan Hillert c , Carl-Gustav Groth g , Ulf Diczfalusy a , Ingemar Bjo È rkhem a, * a Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, Huddinge, SE-141 86 Stockholm, Sweden b Unite  de Nutrition Lipidique, Institut National de la Recherche Agronomique, Dijon, France c Division of Neurology, Karolinska Institutet, Huddinge University Hospital, Huddinge, SE-141 86 Stockholm, Sweden d Division of Geriatric, Karolinska Institutet, Huddinge University Hospital, Huddinge, SE-141 86 Stockholm, Sweden e Department of Clinical Pharmacology, University of Bonn, Bonn, Germany f Department of Psychiatry, Malmo È University Hospital, Malmo È , Sweden g Division of Transplantation Surgery, Karolinska Institutet, Huddinge University Hospital, Huddinge, SE-141 86 Stockholm, Sweden Received 2 August 2000; received in revised form 21 August 2000; accepted 21 August 2000 Abstract The brain is the exclusive or almost exclusive site of formation of 24S-hydroxycholesterol and we have shown that the circulating level of 24S-hydroxycholesterol is dependent upon the relation between cerebral production and hepatic clearance. In the present work we determined plasma levels of 24S-hydroxycholesterol in patients with various neuro- logical diseases. Eleven subjects with brain death occurring 6±10 h before collection of the plasma samples had mark- edly reduced circulating levels of 24S-hydroxycholesterol (243%, P , 0:001). Patients with advanced Alzheimer's disease and cerebral in¯ammatory diseases had slightly lower levels of 24S-hydroxycholesterol in plasma when compared to matched controls. Patients with acute ischemic stroke, multiple sclerosis and primary brain tumors had levels not signi®cantly different from those of controls. The conditions leading to reduced plasma levels of 24S-hydro- xycholesterol had no signi®cant effect on plasma levels of another side-chain oxidized oxysterol, 27-hydroxycholesterol. Except for conditions characterized by very marked destruction of the central nervous system, different severe neuro- logical diseases seem to have relatively small effects on the ¯ux of 24S-hydroxycholesterol from the brain. q 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Alzheimer's disease; Brain; Central nervous system; Neurological diseases; Oxysterols In humans the oxysterol 24S-hydroxycholesterol seems to have an exclusive or almost exclusive origin from the brain [4,6,7] and a speci®c cytochrome P-450 species is involved in the conversion of cholesterol into this compound [6]. In previous work we have shown that there is a net ¯ux of 24S-hydroxycholesterol over the blood±brain barrier into the circulation, which magnitude is about 6 mg/ 24 h [4,7]. Most probably this ¯ux is of importance for cholesterol homeostasis in the brain, and according to in vivo experiments in rats the rate of oxidation of cholesterol into 24S-hydroxycholesterol is similar to the rate of synth- esis of cholesterol in this organ [3]. The unique cerebral origin of 24S-hydroxycholesterol in the circulation has led to the suggestion that the level of this oxysterol may re¯ect disturbed turnover of cholesterol in the brain [4,7]. A demyelination would be expected to cause a transient increase in the ¯ux of 24S-hydroxycholesterol. A destruction of neurons in combination with a loss of myelin occurring during a long time period would, however, be expected to result in decreased circulating levels of 24S- hydroxycholesterol at a later stage of the disease. In addition to cerebral production, there are other factors of importance for the circulating levels of 24S-hydroxycho- lesterol. The distribution of 24S-hydroxycholesterol in the lipoproteins is similar to that of cholesterol [1] and in accor- Neuroscience Letters 293 (2000) 87±90 0304-3940/00/$ - see front matter q 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S0304-3940(00)01466-X www.elsevier.com/locate/neulet * Corresponding author. Tel.: 146-8-585-812-35; fax: 146-8- 585-812-60. E-mail address: ingemar.bjorkhem@chemlab.hs.sll.se (I. Bjo È rkhem).