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Journal of Lipid Research, Vol. 41, 963-974, June 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

Characterization and functional studies of lipoproteins, lipid transfer proteins, and lecithin:cholesterol acyltransferase in CSF of normal individuals and patients with Alzheimer's disease

Correspondence to: C. Labeur

We investigated the lipoprotein distribution and composition in cerebrospinal fluid (CSF) in a group of patients with Alzheimer's disease (AD) or affected by other types of dementia in comparison to non-demented controls. We found slightly decreased apolipoprotein (apo)E and cholesterol concentrations in CSF of AD patients and moderately increased apoA-I concentrations, while in patients suffering from other types of dementia the apoA-I CSF concentration was increased. ApoA-IV concentrations varied widely in human CSF, but were not associated with any clinical condition. HDL₂-like apoE-containing lipoproteins represent the major lipoprotein fraction. In CSF of normal controls, only a minor HDL₃-like apoA-I-containing lipoprotein fraction was observed; this fraction was more prevalent in AD patients. ApoA-II was recovered mostly in the HDL₃ density range, while apoA-IV was not associated with lipoproteins but appeared in a lipid-free form, co-localizing with LCAT immunoreactivity. Bi-dimensional analysis demonstrated pre-ß and apoA-I-containing particles; apoE and apoA-II were detected only in -migrating particles. ApoA-IV distributed both to pre-ß and -migrating particles; the LCAT signal was co-localized in this -migrating fraction. Enzymatically active LCAT was present in human CSF as well as PLTP activity and mass; no CETP mass was detected. In CSF from AD patients, LCAT activity was 50% lower than in CSF from normal controls.

CSF lipoproteins induced a significant cholesterol efflux from cultured rat astrocytes, suggesting that they play an active role in maintaining the cholesterol homeostasis in brain cells.—Demeester, N., G. Castro, C. Desrumaux, C. De Geitere, J. C. Fruchart, P. Santens, E. Mulleners, S. Engelborghs, P. P. De Deyn, J. Vandekerckhove, M. Rosseneu, and C. Labeur. Characterization and functional studies of lipoproteins, lipid transfer proteins, and lecithin:cholesterol acyltransferase in CSF of normal individuals and patients with Alzheimer's disease. J. Lipid Res. 41: 963;–974.

Supplementary key words: cerebrospinal fluid, lipoproteins, Alzheimer's disease, cholesterol, efflux

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