Reelin expression and glycosylation patterns are altered in Alzheimer's disease.
Reelin is a glycoprotein that is essential for the correct cytoarchitectonic organization of the developing CNS. Its function in the adult brain is less understood, although it has been proposed that Reelin is involved in signaling pathways linked to neurodegeneration. Here we analyzed Reelin expression in brains and cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients and nondemented controls. We found a 40% increase in the Reelin protein levels in the cortex of AD patients compared with controls. Similar increases were detected at the Reelin mRNA transcriptional level. This expression correlates with parallel increases in CSF but not in plasma samples. Next, we examined whether CSF Reelin levels were also altered in neurological diseases, including frontotemporal dementia, progressive supranuclear palsy, and Parkinson's disease. The Reelin 180-kDa band increased in all of the neurodegenerative disorders analyzed. Moreover, the 180-kDa Reelin levels correlated positively with Tau protein in CSF. Finally, we studied the pattern of Reelin glycosylation by using several lectins and the anti-HNK-1 antibody. Glycosylation differed in plasma and CSF. Furthermore, the pattern of Reelin lectin binding differed between the CSF of controls and in AD. Our results show that Reelin is up-regulated in the brain and CSF in several neurodegenerative diseases and that CSF and plasma Reelin have distinct cellular origins, thereby supporting that Reelin is involved in the pathogenesis of a number of neurodegenerative diseases.
Botella-López
Arancha
A
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, E-03550 Sant Joan d'Alacant, Spain.
Burgaya
Ferran
F
Gavín
Rosalina
R
García-Ayllón
M Salud
MS
Gómez-Tortosa
Estrella
E
Peña-Casanova
Jordi
J
Ureña
Jesús M
JM
Del Río
José A
JA
Blesa
Rafael
R
Soriano
Eduardo
E
Sáez-Valero
Javier
J
D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D037102:Lectins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D011485:Protein Binding; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D037102:Lectins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases