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. 2009 May;30(5):682-90.
doi: 10.1016/j.neurobiolaging.2007.08.010. Epub 2007 Sep 24.

Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment

Miroslaw Brys  1 , 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
Affiliations

Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment

Miroslaw Brys et al. Neurobiol Aging. 2009 May.

Abstract

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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Figures

Figure 1
Figure 1
Mean values ± standard error of the mean (SEM) of: (A) P-tau231, (B) T-tau, (C) IP and (D) Aβ42/Aβ40 in the diagnostic outcome groups. Legend: Baseline (open) and follow-up (dashed lines). * - follow-up values significantly different than baseline (p<0.01).
Figure 2
Figure 2
Mean ±SEM baseline values for the Aβ42/Aβ40 ratio in E4 carriers and non-carriers by diagnostic group. * - significantly different APOE4 carrier effect within MCI-MCI group (p<0.01).
See this image and copyright information in PMC

References

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