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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. In analogy with the metabolism of lipids in the peripheral circulation, cerebrospinal fluid (CSF) lipids are transported by lipoproteins.
We found slightly decreased apolipoprotein (apo)E and cholesterol concentrations in CSF of AD patients and moderately increased apo A-I concentrations, while in patients suffering from other types of dementia the apo A-I CSF concentration was increased. Although several reports describe the composition of CSF lipoproteins (4, 8–12), their detailed structure and functions are only poorly understood.
Apo E plays an important role in the cholesterol metabolism, both in the peripheral circulation and in the brain, where it is synthesized by astrocytes and glial cells.
It is clearly established that the inheritance of the apolipoprotein (apo) E4 allele is associated with increased risk of developing AD at a younger age (1, 3).
Bi-dimensional analysis demonstrated pre-β and α apo A-I-containing particles; apo E and apo A-II were detected only in α-migrating particles. Such active lipid redistribution might prove to be functionally important because several recent studies have shown that the neuronal membrane cholesterol content influences processing of the amyloid precursor protein (APP) (13–15).
Apo A-IV distributed both to pre-β and γ-migrating particles; the LCAT signal was co-localized in this γ-migrating fraction. Decreasing the neuronal cell cholesterol content, by combining a treatment with lovastatin (HMG-Co A reductase inhibitor) and α-methyl-β-cyclodextrin, reduces amyloid β production.
In order to understand how the HDL particles in the brain compartment are synthesized and remodeled, we investigated in human CSF the presence of minor lipoprotein subclasses such as preβ particles by bi-dimensional non-denaturing gel electrophoresis.
Val and her husband went to Couples Negril, Jamaica in November 2015 to renew t40th-anniversary wedding vows.Apo A-IV concentrations varied widely in human CSF, but were not associated with any clinical condition. CSF lipoproteins are needed for delivery of cholesterol during nerve growth, but it is not known whether they are also actively involved in taking up excess cholesterol from nerve cells.HDL density range, while apo A-IV was not associated with lipoproteins but appeared in a lipid-free form, co-localizing with LCAT immunoreactivity. This cholesterol could then be removed from the CSF via arachnoid granulations or by redistribution to other cells in the brain compartment (9). Several observations suggest a close relationship between the lipoprotein metabolism in the brain and the development of Alzheimer's disease (AD) (1, 2).