Changes in human plasma levels of the brain specific oxysterol 24S-hydroxycholesterol during progression of multiple sclerosis

被引:106
作者
Leoni, V
Masterman, T
Diczfalusy, U
De Luca, G
Hillert, J
Björkhem, I
机构
[1] Univ Insubria, Dept Expt & Clin Biomed Sci DSBSC, Varese, Italy
[2] Huddinge Univ Hosp, Karolinska Inst, Div Clin Chem, SE-14186 Stockholm, Sweden
[3] Huddinge Univ Hosp, Karolinska Inst, Div Neurol, SE-14186 Stockholm, Sweden
关键词
multiple sclerosis; 24S-Hydroxycholesterol; oxysterols; cerebrospinal fluid; magnetic resonance imaging;
D O I
10.1016/S0304-3940(02)00887-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
24S-Hydroxycholesterol (24S-OH-chol) is almost exclusively derived from the brain and the levels of this oxysterol in the circulation may be used as a marker for changes in the turnover of brain cholesterol. In the present study we assayed plasma and cerebrospinal fluid 24S-OH-chol in patients with multiple sclerosis (n = 118) at different stages of the disease. In the oldest groups of patients the levels of 24S-OH-chol were significantly lower than in the controls, possibly reflecting loss of neuronal cells responsible for the synthesis. There was a significant inverse relation between the expanded disability status scale-grade of the disease and the plasma cholesterol related levels of 24S-OH-chol. There was a tendency to increased plasma levels of 24S-OH-chol in the younger patients and almost all of the high levels were found in the patients in the 3rd and 4th decades of life. Increased levels were only found in patients with positive cranial magnetic resonance imaging. The possibility is discussed that plasma levels of 24S-OH-chol may add significantly to existing methods used for evaluation of the different phases of multiple sclerosis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:163 / 166
页数:4
相关论文
共 12 条
[1]   Transport of side-chain oxidized oxysterols in the human circulation [J].
Babiker, A ;
Diczfalusy, U .
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1998, 1392 (2-3) :333-339
[2]  
Björkhem I, 1998, J LIPID RES, V39, P1594
[3]   Plasma levels of 24S-hydroxycholesterol in patients with neurological diseases [J].
Bretillon, L ;
Sidén, Å ;
Wahlund, LO ;
Lütjohann, D ;
Minthon, L ;
Crisby, M ;
Hillert, J ;
Groth, CG ;
Diczfalusy, U ;
Björkhem, I .
NEUROSCIENCE LETTERS, 2000, 293 (02) :87-90
[4]  
Bretillon L, 2000, J LIPID RES, V41, P840
[5]   DETERMINATION OF CHOLESTEROL OXIDATION-PRODUCTS IN HUMAN PLASMA BY ISOTOPE-DILUTION MASS-SPECTROMETRY [J].
DZELETOVIC, S ;
BREUER, O ;
LUND, E ;
DICZFALUSY, U .
ANALYTICAL BIOCHEMISTRY, 1995, 225 (01) :73-80
[6]  
KEEGAN BM, 2000, ANNU REV MED, V53, P285
[7]   cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain [J].
Lund, EG ;
Guileyardo, JM ;
Russell, DW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (13) :7238-7243
[8]  
Lütjohann D, 2000, J LIPID RES, V41, P195
[9]   Cholesterol homeostasis in human brain: Evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation [J].
Lutjohann, D ;
Breuer, O ;
Ahlborg, G ;
Nennesmo, I ;
Siden, A ;
Diczfalusy, U ;
Bjorkhem, I .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (18) :9799-9804
[10]   Medical progress: Multiple sclerosis. [J].
Noseworthy, JH ;
Lucchinetti, C ;
Rodriguez, M ;
Weinshenker, BG .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (13) :938-952