Soluble Megalin is Reduced in Cerebrospinal Fluid Samples of Alzheimer's Disease Patients.
Megalin or low-density lipoprotein receptor-related protein-2 is a member of the low-density lipoprotein receptor family, which has been linked to Alzheimer's disease (AD) by clearing brain amyloid β-peptide (Aβ) across the blood-cerebrospinal fluid barrier at the choroid plexus. Here, we found a soluble form of megalin secreted from choroid plexus epithelial cells. Soluble megalin levels were also localized in the human cerebrospinal fluid (CSF), being reduced in AD patients. We have also shown that soluble megalin binding to Aβ is decreased in the CSF of AD patients, suggesting that decreased sequestration of Aβ in the CSF could be associated with defective clearance of Aβ and an increase of brain Aβ levels. Thus, therapies, which increase megalin expression, at the choroid plexus and/or enhance circulating soluble megalin hold potential to control brain Aβ-related pathologies in AD.
Department of Neurology, Instituto de Investigación Biomédica de Ourense, Pontevedra y Vigo (IBI)/Xerencia de Xestión Integrada de Vigo-SERGAS , Vigo , Spain.
Carlos
C
Spuch
Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) , Madrid , Spain ; Neuroscience Group, Research Institute Hospital , Madrid , Spain.
Desireé
D
Antequera
Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) , Madrid , Spain ; Neuroscience Group, Research Institute Hospital , Madrid , Spain.
Consuelo
C
Pascual
Department of Neurology, Instituto de Investigación Biomédica de Ourense, Pontevedra y Vigo (IBI)/Xerencia de Xestión Integrada de Vigo-SERGAS , Vigo , Spain.
Soledad
S
Abilleira
Department of Neurology, Instituto de Investigación Biomédica de Ourense, Pontevedra y Vigo (IBI)/Xerencia de Xestión Integrada de Vigo-SERGAS , Vigo , Spain.
María
M
Blanco
Department of Neurology, Instituto de Investigación Biomédica de Ourense, Pontevedra y Vigo (IBI)/Xerencia de Xestión Integrada de Vigo-SERGAS , Vigo , Spain.
María José
MJ
Moreno-Carretero
Department of Neurology, Instituto de Investigación Biomédica de Ourense, Pontevedra y Vigo (IBI)/Xerencia de Xestión Integrada de Vigo-SERGAS , Vigo , Spain.
Jesús
J
Romero-López
Department of Histology and Cell Biology, School of Medicine, Kagawa University , Miki , Japan.
Tetsuya
T
Ishida
Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) , Madrid , Spain ; Service of Neurology, Research Institute Hospital , Madrid , Spain.
Jose Antonio
JA
Molina
Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) , Madrid , Spain ; Service of Neurology, Research Institute Hospital , Madrid , Spain.
Alberto
A
Villarejo
Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) , Madrid , Spain ; Service of Neurology, Research Institute Hospital , Madrid , Spain.
Felix
F
Bermejo-Pareja
Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) , Madrid , Spain ; Neuroscience Group, Research Institute Hospital , Madrid , Spain.
Eva
E
Carro
Alzheimer’s disease; amyloid β; cerebrospinal fluid; choroid plexus; clearance; epithelial cells; megalin; patients