Plasma phosphorylated TDP-43 levels are elevated in patients with frontotemporal dementia carrying a C9orf72 repeat expansion or a GRN mutation
Por:
Suarez-Calvet, M, Dols-Icardo, O, Llado, A, Sanchez-Valle, R, Hernandez, I, Amer, G, Anton-Aguirre, S, Alcolea, D, Fortea, J, Ferrer, I, van der Zee, J, Dillen, L, Van Broeckhoven, C, Molinuevo, JL, Blesa, R, Clarimon, J, Lleo, A
Publicada:
1 jun 2014
Resumen:
Objectives About a half of patients with frontotemporal dementia (FTD) has deposition of phosphorylated TDP-43 protein (pTDP-43) in the brain. We studied pTDP-43 and total TDP-43 levels in plasma and cerebrospinal fluid (CSF) in healthy controls and patients with FTD, including those carrying a repeat expansion in the C9orf72 gene or a mutation in GRN.
Methods We included 88 plasma samples of 10 C9orf72 expansion carriers, 5 GRN mutation carriers, 51 patients with FTD without a known mutation and 22 healthy controls. We also obtained CSF samples from 25 patients with FTD (2 with C9orf72 expansion and 3 with a GRN mutation) and 22 healthy controls. We measured pTDP-43 and total TDP-43 levels using sandwich ELISA.
Results Patients carrying the C9orf72 repeat expansion or a GRN mutation had significantly higher plasma and CSF levels of pTDP-43 than the remaining patients with FTD (p<0.05). In addition, plasma pTDP-43 levels were higher in patients with FTD carrying a C9orf72 expansion or GRN mutations than in healthy controls (p<0.05).
Conclusions Our study shows that plasma pTDP-43 levels may be increased in some genetic forms of FTD known to be associated with TDP-43 proteinopathies.
Filiaciones:
Suarez-Calvet, M:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, E-08193 Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Dols-Icardo, O:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, E-08193 Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Llado, A:
Hosp Clin Barcelona, Alzheimers Dis & Other Cognit Disorders Unit, Dept Neurol, Barcelona, Spain
Sanchez-Valle, R:
Hosp Clin Barcelona, Alzheimers Dis & Other Cognit Disorders Unit, Dept Neurol, Barcelona, Spain
Hernandez, I:
Fundacio ACE, Memory Clin, Inst Catala Neurociencies Aplicades, Barcelona, Spain
Amer, G:
Hosp Univ Son Espases, Dept Neurol, Mallorca, Spain
Anton-Aguirre, S:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, E-08193 Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Alcolea, D:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, E-08193 Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Fortea, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, E-08193 Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Ferrer, I:
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Univ Barcelona, Hosp Univ Bellvitge, IDIBELL, Inst Neuropatol,Serv Anat Patol, Barcelona, Spain
van der Zee, J:
VIB, Neurodegenerat Brain Dis Grp, Dept Mol Genet, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium
Dillen, L:
VIB, Neurodegenerat Brain Dis Grp, Dept Mol Genet, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium
Van Broeckhoven, C:
VIB, Neurodegenerat Brain Dis Grp, Dept Mol Genet, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium
Molinuevo, JL:
Hosp Clin Barcelona, Alzheimers Dis & Other Cognit Disorders Unit, Dept Neurol, Barcelona, Spain
Blesa, R:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, E-08193 Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Clarimon, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, E-08193 Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Lleo, A:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, E-08193 Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
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