title: Characterization and functional studies of lipoproteins, lipid transfer proteins, and lecithin:cholesterol acyltransferase in CSF of normal individuals and patients with Alzheimer's disease.
abstract: 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. HDL(2)-like apoE-containing lipoproteins represent the major lipoprotein fraction. In CSF of normal controls, only a minor HDL(3)-like apoA-I-containing lipoprotein fraction was observed; this fraction was more prevalent in AD patients. ApoA-II was recovered mostly in the HDL(3) 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-beta and alpha apoA-I-containing particles; apoE and apoA-II were detected only in alpha-migrating particles. ApoA-IV distributed both to pre-beta and gamma-migrating particles; the LCAT signal was co-localized in this gamma-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.
authors.affiliation: Department of Biochemistry, University of Gent, B-9000 Gent, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Demeester
authors.forename: G
authors.initials: G
authors.lastname: Castro
authors.forename: C
authors.initials: C
authors.lastname: Desrumaux
authors.forename: C
authors.initials: C
authors.lastname: De Geitere
authors.forename: J C
authors.initials: JC
authors.lastname: Fruchart
authors.forename: P
authors.initials: P
authors.lastname: Santens
authors.forename: E
authors.initials: E
authors.lastname: Mulleners
authors.forename: S
authors.initials: S
authors.lastname: Engelborghs
authors.forename: P P
authors.initials: PP
authors.lastname: De Deyn
authors.forename: J
authors.initials: J
authors.lastname: Vandekerckhove
authors.forename: M
authors.initials: M
authors.lastname: Rosseneu
authors.forename: C
authors.initials: C
authors.lastname: Labeur
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D002352:Carrier Proteins / Q000134:cerebrospinal fluid*; D016022:Case-Control Studies; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000134:cerebrospinal fluid*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000134:cerebrospinal fluid*; D051381:Rats; D014461:Ultracentrifugation
chemical_list: D002352:Carrier Proteins; D008074:Lipoproteins; C030363:lipid transfer protein; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase