Plasma phosphorylated TDP-43 levels are elevated in patients with frontotemporal dementia carrying a C9orf72 repeat expansion or a GRN mutation

Marc Suárez-Calvet, Oriol Dols-Icardo, Albert Lladó, Raquel Sánchez-Valle, Isabel Hernández, Guillermo Amer, Sofía Antón-Aguirre, Daniel Alcolea, Juan Fortea, Isidre Ferrer, Julie Van Der Zee, Lubina Dillen, Christine Van Broeckhoven, José Luís Molinuevo, Rafael Blesa, Jordi Clarimón, Alberto Lleó

Research output: Contribution to journalArticleResearchpeer-review

41 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)684-691
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume85
Issue number6
DOIs
Publication statusPublished - 1 Jun 2014

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