Received on May 19, 2006
Accepted on August 15, 2006

Lipids, Lipoproteins, and Cardiovascular Risk Factors

Lipoprotein(a) in the Cerebrospinal Fluid of Neurological Patients with Blood-Cerebrospinal Fluid Barrier Dysfunction

¹ Department of Biochemistry and Molecular Biology, University of Bari, and Institute of Biomembrane and BioEnergetics, Consiglio Nazionale delle Ricerche, Rome, Italy
² Department of Biochemistry and Molecular Biology, University of Bari
³ Department of Neurology, University of Florence, Italy
⁴ INSERM, Paris, France

^* To whom correspondence should be addressed. E-mail: g.pepe{at}biologia.uniba.it.

Background: Lipoprotein(a) [Lp(a)] is a recognized pathogenic particle in human plasma, but its presence in the cerebrospinal fluid and its possible role in the central nervous system have not been documented. We tested the hypothesis that apolipoprotein(a) [apo(a)], free or as a component of the Lp(a) particle, can cross the blood-cerebrospinal fluid barrier and be found in the cerebrospinal fluid of patients affected by neurologic pathologies.

Methods: We studied paired cerebrospinal fluid/serum samples from 77 patients with inflammatory (n = 20) or noninflammatory (n = 34) blood-cerebrospinal fluid barrier dysfunction and from 22 patients without blood-cerebrospinal fluid barrier dysfunction. We used ELISA to measure Lp(a) concentrations and Western blot and immunodetection to analyze apo(a) isoforms in native and reducing conditions.

Results: Entire Lp(a) with either small or large apo(a) isoforms was present in the cerebrospinal fluid of patients with blood-cerebrospinal fluid barrier dysfunction, regardless of its pathogenesis. Multiple linear regression analysis showed that both serum Lp(a) concentration (P = 0.003) and cerebrospinal fluid/serum albumin ratio (P <0.001) were predictors of the Lp(a) concentration in cerebrospinal fluid.

Conclusions: Our results demonstrate that Lp(a) can cross a dysfunctional blood-cerebrospinal fluid barrier. The unusual presence of Lp(a) in the cerebrospinal fluid could extend some of its known pathogenic effects to the central nervous system.