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 cerebrospin al fluid (CSF) in a group of patients with Alzheimer's disease (AD) or affe cted by other types of dementia in comparison to non-demented controls. We found slightly decreased apolipoprotein (apo)E and cholesterol concentratio ns in CSF of AD patients and moderately increased apoA-I concentrations, wh ile in patients suffering from other types of dementia the apoA-I CSF conce ntration was increased. ApoA-IV concentrations varied widely in human CSF, but were not associated with any clinical condition. HDL2-like apoE-contain ing lipoproteins represent the major lipoprotein fraction. In CSF of normal controls, only a minor HDL3-like apoA-I-containing lipoprotein fraction wa s observed; this fraction was more prevalent in AD patients. ApoA-II was re covered mostly in the HDL3 density range, while apoA-IV was not associated with lipoproteins but appeared in a lipid-free form, co-localizing with LCA T 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-P and gamma-migrating particles; the LCAT signal was co-localized in this gamma-migrating fractio n. Enzymatically active LCAT tvas present in human CSF as well as PLTP acti vity and mass; no CETP mass was detected. In CSF from AD patients, LCAT act ivity was 50% lower than in CSF from normal controls. CSF lipoproteins indu ced a significant cholesterol efflux from cultured rat astrocytes, suggesti ng that they play an active role in maintaining the cholesterol homeostasis in brain cells.