Lipoprotein(a) in the cerebrospinal fluid of neurological patients with blood-cerebrospinal fluid barrier dysfunction.
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 without blood-cerebrospinal fluid barrier dysfunction (n=23). 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.
Pepe
Gabriella
G
Department of Biochemistry and Molecular Biology, University of Bari, Italy. g.pepe@biologia.uniba.it
Chimienti
Guglielmina
G
Liuzzi
Grazia Maria
GM
Lamanuzzi
Biagia Leila
BL
Nardulli
Marina
M
Lolli
Francesco
F
Anglés-Cano
Eduardo
E
Matà
Sabrina
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D001812:Blood-Brain Barrier / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid* / Q000473:pathology / Q000503:physiopathology*; D011237:Predictive Value of Tests; D020033:Protein Isoforms / Q000134:cerebrospinal fluid
D017270:Lipoprotein(a); D020033:Protein Isoforms