title: Multicenter assessment of CSF-phosphorylated tau for the prediction of conversion of MCI.
abstract: BACKGROUND
  The measurement of hyperphosphorylated tau (p-tau) in CSF has been proposed as a biomarker candidate for the prediction of Alzheimer disease (AD) in patients with mild cognitive impairment (MCI). However, a standard quantitative criterion of p-tau has not been evaluated.
  
  
  OBJECTIVE
  To assess in a multicenter study the predictive accuracy of an a priori defined criterion of tau phosphorylated at threonine 231 (p-tau(231)) for the prediction of conversion from MCI to AD during a short-term observation interval.
  
  
  METHODS
  The study included 43 MCI converters, 45 stable MCI (average follow-up interval = 1.5 years), and 57 healthy controls (at baseline only). Subjects were recruited at four international expert sites in a retrospective study design. Cox regression models stratified according to center were used to predict conversion status. Bootstrapped 95% CIs of classification accuracy were computed.
  
  
  RESULTS
  Levels of p-tau(231) were a significant predictor of conversion (B = 0.026, p = 0.001), independent of age, gender, Mini-Mental State Examination, and ApoE genotype. For an a priori-defined cutoff point (27.32 pg/mL), sensitivity ranged between 66.7 and 100% and specificity between 66.7 and 77.8% among centers. The bootstrapped mean percentage of correctly classified cases was 79.95% (95% CI = 79.9 to 80.00%). Post hoc defined cutoff values yielded a mean bootstrapped classification accuracy of 80.45% (95% CI = 80.24 to 80.76%).
  
  
  CONCLUSIONS
  An a priori defined cutoff value of p-tau(231) yields relatively stable results across centers, suggesting a good feasibility of a standard criterion of p-tau(231) for the prediction of Alzheimer disease.
authors: Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany.
authors: M
authors: M
authors: Ewers
authors: K
authors: K
authors: Buerger
authors: S J
authors: SJ
authors: Teipel
authors: P
authors: P
authors: Scheltens
authors: J
authors: J
authors: Schröder
authors: R P
authors: RP
authors: Zinkowski
authors: F H
authors: FH
authors: Bouwman
authors: P
authors: P
authors: Schönknecht
authors: N S M
authors: NS
authors: Schoonenboom
authors: N
authors: N
authors: Andreasen
authors: A
authors: A
authors: Wallin
authors: J F
authors: JF
authors: DeBernardis
authors: D J
authors: DJ
authors: Kerkman
authors: B
authors: B
authors: Heindl
authors: K
authors: K
authors: Blennow
authors: H
authors: H
authors: Hampel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D003430:Cross-Sectional Studies; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016875:tau Proteins