title: An unbiased, staged, multicentre, validation strategy for Alzheimer's disease CSF tau levels.
abstract: Newly proposed diagnostic criteria for Alzheimer's disease include cerebrospinal fluid (CSF) tau levels as one core supportive criterion. The published high sensitivity and specificity figures for CSF tau levels in Alzheimer's disease are offset by the large range of proposed cutoff values (9.6 pg/mL to 1140 pg/mL). This study aimed to provide guidance on how to establish, validate and audit CSF tau cutoff values using an unbiased, two-stage multicentre strategy. Both receiver operator characteristics (ROC) optimised and population-based cutoff values were calculated on a pilot dataset (n=99), validated in a large dataset (n=560) and then compared to the literature. The data suggest using an ROC optimised cutoff level of 323+/-51.7 pg/mL allowing for the published inter-laboratory coefficient of variation of 16%. This cutoff level was confirmed in a prospective audit (n=100). As demand for CSF tau levels will increase globally, the accuracy of local CSF hTau cutoff levels can be compared against this benchmark.
authors.affiliation: Department of Neuroimmunology, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. a.petzold@ion.ucl.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Petzold
authors.forename: M D
authors.initials: MD
authors.lastname: Chapman
authors.forename: S
authors.initials: S
authors.lastname: Schraen
authors.forename: N A
authors.initials: NA
authors.lastname: Verwey
authors.forename: F
authors.initials: F
authors.lastname: Pasquier
authors.forename: S
authors.initials: S
authors.lastname: Bombois
authors.forename: J
authors.initials: J
authors.lastname: Brettschneider
authors.forename: N C
authors.initials: NC
authors.lastname: Fox
authors.forename: C A F
authors.initials: CA
authors.lastname: von Arnim
authors.forename: C
authors.initials: C
authors.lastname: Teunissen
authors.forename: Y
authors.initials: Y
authors.lastname: Pijnenburg
authors.forename: M W
authors.initials: MW
authors.lastname: Riepe
authors.forename: M
authors.initials: M
authors.lastname: Otto
authors.forename: H
authors.initials: H
authors.lastname: Tumani
authors.forename: P
authors.initials: P
authors.lastname: Scheltens
authors.forename: L
authors.initials: L
authors.lastname: Buee
authors.forename: M N
authors.initials: MN
authors.lastname: Rossor
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D019985:Benchmarking; D002624:Chemistry, Clinical / Q000379:methods / Q000592:standards*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011786:Quality Control; D012372:ROC Curve; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins