Disease-Specific Changes in Reelin Protein and mRNA in Neurodegenerative Diseases
Lidón, Laia (Universitat de Barcelona. Institut de Neurociències)
Urrea, Laura (Universitat de Barcelona. Institut de Neurociències)
Llorens, Franc (Institut d'Investigació Biomèdica de Bellvitge)
Gil, Vanessa (Universitat de Barcelona. Institut de Neurociències)
Alvarez, Ignacio (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Diez-Fairen, Monica (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Aguilar Barberà, Miquel (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Pastor, Pau (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Zerr, Inga (German Center for Neurodegenerative Diseases)
Alcolea, Daniel (Institut d'Investigació Biomèdica Sant Pau)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Vidal Barba, Enric (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Gavín, Rosalina (Universitat de Barcelona. Institut de Neurociències)
Ferrer, Isidro (Institut d'Investigació Biomèdica de Bellvitge)
Del Rio, Jose Antonio (Universitat de Barcelona. Institut de Neurociències)

Date:	2020
Abstract:	Reelin is an extracellular glycoprotein that modulates neuronal function and synaptic plasticity in the adult brain. Decreased levels of Reelin activity have been postulated as a key factor during neurodegeneration in Alzheimer's disease (AD) and in aging. Thus, changes in levels of full-length Reelin and Reelin fragments have been revealed in cerebrospinal fluid (CSF) and in post-mortem brains samples of AD patients with respect to non-AD patients. However, conflicting studies have reported decreased or unchanged levels of full-length Reelin in AD patients compared to control (nND) cases in post-mortem brains and CSF samples. In addition, a compelling analysis of Reelin levels in neurodegenerative diseases other than AD is missing. In this study, we analyzed brain levels of RELN mRNA and Reelin protein in post-mortem frontal cortex samples from different sporadic AD stages, Parkinson's disease with dementia (PDD), and Creutzfeldt-Jakob disease (sCJD), obtained from five different Biobanks. In addition, we measured Reelin protein levels in CSF samples of patients with mild cognitive impairment (MCI), dementia, or sCJD diagnosis and a group of neurologically healthy cases. The results indicate an increase in RELN mRNA in the frontal cortex of advanced stages of AD and in sCJD(I) compared to controls. This was not observed in PDD and early AD stages. However, Reelin protein levels in frontal cortex samples were unchanged between nND and advanced AD stages and PDD. Nevertheless, they decreased in the CSF of patients with dementia in comparison to those not suffering with dementia and patients with MCI. With respect to sCJD, there was a tendency to increase in brain samples in comparison to nND and to decrease in the CSF with respect to nND. In conclusion, Reelin levels in CSF cannot be considered as a diagnostic biomarker for AD or PDD. However, we feel that the CSF Reelin changes observed between MCI, patients with dementia, and sCJD might be helpful in generating a biomarker signature in prodromal studies of unidentified dementia and sCJD.
Grants:	Ministerio de Ciencia, Innovación y Universidades RTI2018-099773-B-I00 Instituto de Salud Carlos III PI19-00144
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Reelin ; Creutzfeldt-Jakob disease ; Alzheimer's disease ; Parkinson's disease dementia ; A-synucleopathies ; Cerebrospinal fluid
Published in:	Cells, Vol. 9 (may 2020) , ISSN 2073-4409

DOI: 10.3390/cells9051252
PMID: 32438605

18 p, 2.5 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Centre de Recerca en Sanitat Animal (CReSA-IRTA)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles