Multicenter assessment of CSF-phosphorylated tau for the prediction of conversion of MCI.
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.
Ewers
M
M
Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany.
Buerger
K
K
Teipel
S J
SJ
Scheltens
P
P
Schröder
J
J
Zinkowski
R P
RP
Bouwman
F H
FH
Schönknecht
P
P
Schoonenboom
N S M
NS
Andreasen
N
N
Wallin
A
A
DeBernardis
J F
JF
Kerkman
D J
DJ
Heindl
B
B
Blennow
K
K
Hampel
H
H
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*
D016875:tau Proteins