title: Total tau and phosphorylated tau 181 levels in the cerebrospinal fluid of patients with frontotemporal dementia due to P301L and G272V tau mutations.
abstract: BACKGROUND
  Frontotemporal dementia (FTD) is a pathologically heterogeneous group of presenile neurodegenerative disorders, with or without the deposition of hyperphosphorylated tau protein in affected brain regions. Mutations in the tau gene have been found in the familial form of FTD, linked to chromosome 17q21-22, showing a spectrum of tauopathy.
  
  
  OBJECTIVE
  To evaluate levels of total tau, phosphorylated tau 181 (Ptau-181), and amyloid-beta1-42 in the cerebrospinal fluid (CSF) of patients with FTD, with special emphasis on FTD due to tau mutations.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Outpatient neurology clinics at 2 university medical centers, in Rotterdam and Amsterdam (the Netherlands).
  
  
  METHODS
  Twenty-six patients with FTD (9 with tau mutations 7 P301L and 2 G272V), 18 patients with Alzheimer disease (AD), and 13 nondemented controls.
  
  
  METHODS
  Total tau, Ptau-181, and amyloid-beta1-42 levels in CSF, obtained by lumbar puncture, were determined by sandwich enzyme-linked immunosorbent assay. Patients were diagnosed after clinical examination, neuropsychologic evaluation, and neuroimaging. Differences between patient groups were statistically evaluated using nonparametric tests.
  
  
  RESULTS
  Although CSF levels of total tau were mildly increased in FTD patients compared with nondemented controls (P =.05), median CSF total tau levels were low in the subgroup with tau mutations compared with AD patients. Furthermore, CSF levels of Ptau-181 and amyloid-beta1-42 were not different in FTD patients, including the patients with tau mutations, compared with nondemented controls.
  
  
  CONCLUSIONS
  The tauopathy in P301L and G272V does not appear to be associated with an evident increase in CSF levels of Ptau-181 in FTD patients with these tau mutations, in contrast with findings in patients with AD.
authors.affiliation: Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands. s.rosso@erasmusmc.nl
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Rosso
authors.forename: Esther
authors.initials: E
authors.lastname: van Herpen
authors.forename: Yolande A L
authors.initials: YA
authors.lastname: Pijnenburg
authors.forename: Niki S M
authors.initials: NS
authors.lastname: Schoonenboom
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Peter
authors.initials: P
authors.lastname: Heutink
authors.forename: John C
authors.initials: JC
authors.lastname: van Swieten
mesh_terms: D000368:Aged; D001284:Atrophy / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004252:DNA Mutational Analysis; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000235:genetics* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D015870:Gene Expression / Q000235:genetics*; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D010766:Phosphorylation; D017354:Point Mutation / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000134:cerebrospinal fluid*; D013702:Temporal Lobe / Q000473:pathology; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics
chemical_list: D016875:tau Proteins; D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; C080888:tau-protein kinase