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Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment.

Journal article
Authors Miroslaw Brys
Elizabeth Pirraglia
Kenneth Rich
Sindre Rolstad
Lisa Mosconi
Remigiusz Switalski
Lidia Glodzik-Sobanska
Susan De Santi
Ray Zinkowski
Pankaj Mehta
Domenico Pratico
Leslie A Saint Louis
Anders Wallin
Kaj Blennow
Mony J de Leon
Published in Neurobiology of aging
Volume 30
Issue 5
Pages 682-90
ISSN 1558-1497
Publication year 2009
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 682-90
Language en
Keywords Aged, Aged, 80 and over, Alzheimer Disease, cerebrospinal fluid, diagnosis, Amyloid beta-Protein, analysis, cerebrospinal fluid, Biological Markers, analysis, cerebrospinal fluid, Cognition Disorders, cerebrospinal fluid, diagnosis, Cohort Studies, Disease Progression, Early Diagnosis, Female, Humans, Isoprostanes, analysis, cerebrospinal fluid, Longitudinal Studies, Male, Middle Aged, Peptide Fragments, analysis, cerebrospinal fluid, Predictive Value of Tests, Prognosis, tau Proteins, analysis, cerebrospinal fluid
Subject categories Medical and Health Sciences


OBJECTIVES: 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.

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