Disease-Specific Changes in Reelin Protein and mRNA in Neurodegenerative Diseases
Por:
Lidon, L, Urrea, L, Llorens, F, Gil, V, Alvarez, I, Diez-Fairen, M, Aguilar, M, Pastor, P, Zerr, I, Alcolea, D, Lleo, A, Vidal, E, Gavin, R, Ferrer, I, Del Rio, JA
Publicada:
1 may 2020
Resumen:
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.
Filiaciones:
Lidon, L:
Barcelona Inst Sci & Technol BIST, Inst Bioengn Catalonia IBEC, Mol & Cellular Neurobiotechnol, Sci Pk Barcelona, Barcelona 08028, Spain
Univ Barcelona, Dept Cell Biol Physiol & Immunol, Fac Biol, Barcelona 08028, Spain
Ctr Networked Biomed Res Neurodegenerat Dis Ciber, Barcelona 28031, Spain
Univ Barcelona, Inst Neurosci, Barcelona 08028, Spain
Urrea, L:
Barcelona Inst Sci & Technol BIST, Inst Bioengn Catalonia IBEC, Mol & Cellular Neurobiotechnol, Sci Pk Barcelona, Barcelona 08028, Spain
Univ Barcelona, Dept Cell Biol Physiol & Immunol, Fac Biol, Barcelona 08028, Spain
Ctr Networked Biomed Res Neurodegenerat Dis Ciber, Barcelona 28031, Spain
Univ Barcelona, Inst Neurosci, Barcelona 08028, Spain
Llorens, F:
Ctr Networked Biomed Res Neurodegenerat Dis Ciber, Barcelona 28031, Spain
Univ Med Gottingen, Dept Neurol, D-37075 Gottingen, Germany
Bellvitge Biomed Res Inst IDIBELL, Lhospitalet De Llobregat 08908, Llobregat, Spain
Gil, V:
Barcelona Inst Sci & Technol BIST, Inst Bioengn Catalonia IBEC, Mol & Cellular Neurobiotechnol, Sci Pk Barcelona, Barcelona 08028, Spain
Univ Barcelona, Dept Cell Biol Physiol & Immunol, Fac Biol, Barcelona 08028, Spain
Ctr Networked Biomed Res Neurodegenerat Dis Ciber, Barcelona 28031, Spain
Univ Barcelona, Inst Neurosci, Barcelona 08028, Spain
Alvarez, I:
Fundacio Recerca Biomed & Social Mutua Terrassa, Barcelona 08221, Spain
Hosp Univ Mutua Terrassa, Dept Neurol, Memory Disorders Unit, Barcelona 08221, Spain
Diez-Fairen, M:
Fundacio Recerca Biomed & Social Mutua Terrassa, Barcelona 08221, Spain
Hosp Univ Mutua Terrassa, Dept Neurol, Memory Disorders Unit, Barcelona 08221, Spain
Aguilar, M:
Fundacio Recerca Biomed & Social Mutua Terrassa, Barcelona 08221, Spain
Hosp Univ Mutua Terrassa, Dept Neurol, Memory Disorders Unit, Barcelona 08221, Spain
Pastor, P:
Fundacio Recerca Biomed & Social Mutua Terrassa, Barcelona 08221, Spain
Hosp Univ Mutua Terrassa, Dept Neurol, Memory Disorders Unit, Barcelona 08221, Spain
Zerr, I:
Univ Med Gottingen, Dept Neurol, D-37075 Gottingen, Germany
German Ctr Neurodegenerat Dis, D-37075 Gottingen, Germany
Alcolea, D:
Ctr Networked Biomed Res Neurodegenerat Dis Ciber, Barcelona 28031, Spain
Univ Autonoma Barcelona, Inst Invest Biomed St Pau, Dept Neurol, Memory Unit,Hosp St Pau, Barcelona 08041, Spain
Lleo, A:
Ctr Networked Biomed Res Neurodegenerat Dis Ciber, Barcelona 28031, Spain
Univ Autonoma Barcelona, Inst Invest Biomed St Pau, Dept Neurol, Memory Unit,Hosp St Pau, Barcelona 08041, Spain
Vidal, E:
UAB, IRTA, Ctr Recerca Sanitat Anim CReSA, Campus Univ Autonoma Barcelona, Bellaterra 08193, Catalonia, Spain
Gavin, R:
Barcelona Inst Sci & Technol BIST, Inst Bioengn Catalonia IBEC, Mol & Cellular Neurobiotechnol, Sci Pk Barcelona, Barcelona 08028, Spain
Univ Barcelona, Dept Cell Biol Physiol & Immunol, Fac Biol, Barcelona 08028, Spain
Ctr Networked Biomed Res Neurodegenerat Dis Ciber, Barcelona 28031, Spain
Univ Barcelona, Inst Neurosci, Barcelona 08028, Spain
Ferrer, I:
Ctr Networked Biomed Res Neurodegenerat Dis Ciber, Barcelona 28031, Spain
Univ Barcelona, Inst Neurosci, Barcelona 08028, Spain
Univ Barcelona, Dept Pathol & Expt Therapeut, Barcelona 08907, Spain
Bellvitge Univ Hosp, Barcelona 08907, Spain
Bellvitge Biomed Res Inst IDIBELL, Barcelona 08908, Spain
Del Rio, JA:
Barcelona Inst Sci & Technol BIST, Inst Bioengn Catalonia IBEC, Mol & Cellular Neurobiotechnol, Sci Pk Barcelona, Barcelona 08028, Spain
Univ Barcelona, Dept Cell Biol Physiol & Immunol, Fac Biol, Barcelona 08028, Spain
Ctr Networked Biomed Res Neurodegenerat Dis Ciber, Barcelona 28031, Spain
Univ Barcelona, Inst Neurosci, Barcelona 08028, Spain
Gold, Green Published
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