Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment.
OBJECTIVE
To longitudinally evaluate five cerebrospinal fluid (CSF) biomarkers in the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD).


METHODS
A baseline and 2-year follow-up clinical and CSF study of 86 subjects, including 22 MCI patients that declined to AD (MCI-AD), 43 MCI that did not deteriorate (MCI-MCI) and 21 controls (NL-NL). All subjects were studied for total and phosphorylated tau (T-tau, P-tau(231)), amyloid beta (Abeta) Abeta(42)/Abeta(40) ratio, isoprostane (IP) as well as P-tau(231)/Abeta(42/40) and T-tau/Abeta(42/40) ratios.


RESULTS
At baseline and at follow-up MCI-AD showed higher levels P-tau(231), T-tau, IP, P-tau(231)/Abeta(42/40) and T-tau/Abeta(42/40) ratios and lower Abeta(42)/Abeta(40) than MCI-MCI or NL-NL. Baseline P-tau(231) best predicted MCI-AD (80%, p<0.001) followed in accuracy by P-tau(231)/Abeta(42/40) and T-tau/Abeta(42/40) ratios (both 75%, p's<0.001), T-tau (74%, p<0.001), Abeta(42)/Abeta(40) (69%, p<0.01), and IP (68%, p<0.01). Only IP showed longitudinal effects (p<0.05).


CONCLUSIONS
P-tau(231) is the strongest predictor of the decline from MCI to AD. IP levels uniquely show longitudinal progression effects. These results suggest the use of CSF biomarkers in secondary prevention trials.
Brys
Miroslaw
M
New York University School of Medicine, NY, USA.
Pirraglia
Elizabeth
E
Rich
Kenneth
K
Rolstad
Sindre
S
Mosconi
Lisa
L
Switalski
Remigiusz
R
Glodzik-Sobanska
Lidia
L
De Santi
Susan
S
Zinkowski
Ray
R
Mehta
Pankaj
P
Pratico
Domenico
D
Saint Louis
Leslie A
LA
Wallin
Anders
A
Blennow
Kaj
K
de Leon
Mony J
MJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015331:Cohort Studies; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D028421:Isoprostanes / Q000032:analysis / Q000134:cerebrospinal fluid; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D011379:Prognosis; D016875:tau Proteins / Q000032:analysis / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D028421:Isoprostanes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins