Characterization and functional studies of lipoproteins, lipid transfer proteins, and lecithin:cholesterol acyltransferase in CSF of normal individuals and patients with Alzheimer's disease.
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.
Demeester
N
N
Department of Biochemistry, University of Gent, B-9000 Gent, Belgium.
Castro
G
G
Desrumaux
C
C
De Geitere
C
C
Fruchart
J C
JC
Santens
P
P
Mulleners
E
E
Engelborghs
S
S
De Deyn
P P
PP
Vandekerckhove
J
J
Rosseneu
M
M
Labeur
C
C
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
D002352:Carrier Proteins; D008074:Lipoproteins; C030363:lipid transfer protein; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase