title: Csf p-tau181/tau ratio as biomarker for TDP pathology in frontotemporal dementia.
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.
authors.affiliation: Centre of Neurodegenerative Disorders, Neurology Unit, University of Brescia , Brescia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.forename: Alberto
authors.initials: A
authors.lastname: Benussi
authors.forename: Silvana
authors.initials: S
authors.lastname: Archetti
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Lucilla
authors.initials: L
authors.lastname: Parnetti
authors.forename: Benedetta
authors.initials: B
authors.lastname: Nacmias
authors.forename: Sandro
authors.initials: S
authors.lastname: Sorbi
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D004268:DNA-Binding Proteins; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Amyloid beta-peptides/cerebrospinal fluid; biological markers/cerebrospinal fluid; frontotemporal lobar degeneration/cerebrospinal fluid; peptide fragments/cerebrospinal fluid; tau proteins/cerebrospinal fluid