Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment

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 (AP) A beta(42)/A beta(40) ratio, isoprostane (IP) as well as P-tau(231)/A beta(42/40) and T-tau/A beta(42/40) ratios. Results: At baseline and at follow-up MCI-AD showed higher levels P-tau(231), T-tau, IP, P-tau(231)/A beta(42/40) and T-tau/A beta(42/40) ratios and lower A beta(42)/A beta(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)/A beta(42/40) and T-tau/A beta(42/40) ratios (both 75%, p's < 0.001), T-tau (74%, p < 0.001), A beta(42)/A beta(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. (C) 2007 Elsevier Inc. All rights reserved.