Csf p-tau181/tau ratio as biomarker for TDP pathology in frontotemporal dementia

Barbara Borroni, Alberto Benussi, Silvana Archetti, Daniela Galimberti, Lucilla Parnetti, Benedetta Nacmias, Sandro Sorbi, Elio Scarpini, Alessandro Padovani

Research output: Contribution to journalArticlepeer-review

Abstract

Our objective was to evaluate the CSF phospho-Tau181/total-Tau (p/t-Tau) ratio to distinguish between the two main forms of frontotemporal lobar degeneration (FTLD): FTLD with TDP-43 (FTLD-TDP) and FTLD with Tau inclusions (FTLD-Tau). CSF p/t-Tau ratio was examined in 79 FTLD patients with predictable neuropathology, i.e. Tau (affected by progressive supranuclear palsy or carriers of mutations within the MAPT gene) or TDP-43 (carriers of mutations within granulin, C9orf72, TARDBP genes or affected by FTD with motor neuron disease). FTLD patients were randomly grouped in a training cohort (n = 39) to assess the best CSF p/t-Tau cut-off score according to ROC analysis, and a validation cohort (n = 40) to evaluate accuracy values of the identified marker. Results showed that, in the training cohort, we found a significantly reduced CSF p/t-Tau ratio in FTLD-TDP relative to FTLD-Tau. ROC analysis for p/t-Tau ratio was 0.873 and cut-off score of 0.136 allowed to differentiate FTLD-TDP and FTLD-Tau with 81.8% sensitivity and 88.2% specificity, respectively. Analysis in the validation cohort showed CSF p/t-Tau ratio <0.136 to distinguish FTLD-TDP from FTLD-Tau with 83.3% specificity and 63.6% sensitivity, respectively. The positive predictive value of detecting TDP neuropathology was 82.4%. In conclusion, a reduced CSF p/t-Tau ratio represents a viable biomarker to correctly identify TDP pathology in FTLD.

Original languageEnglish
Pages (from-to)86-91
Number of pages6
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Volume16
Issue number1-2
DOIs
Publication statusPublished - Mar 1 2015

Keywords

  • Amyloid beta-peptides/cerebrospinal fluid
  • Biological markers/cerebrospinal fluid
  • Frontotemporal lobar degeneration/cerebrospinal fluid
  • Peptide fragments/cerebrospinal fluid
  • Tau proteins/cerebrospinal fluid

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)

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