Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment

Brys, Miroslaw; Pirraglia, Elizabeth; Rich, Kenneth; Rolstad, Sindre; Mosconi, Lisa; Switalski, Remigiusz; Glodzik-Sobanska, Lidia; De Santi, Susan; Zinkowski, Ray; Mehta, Pankaj; Pratico, Domenico; Saint Louis, Leslie A.; Wallin, Anders; Blennow, Kaj; de Leon, Mony J.

doi:10.1016/j.neurobiolaging.2007.08.010

« Previous Next »Neurobiology of Aging
Volume 30, Issue 5 , Pages 682-690, May 2009

Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment

Miroslaw Brys
- New York University School of Medicine, NY, USA
Elizabeth Pirraglia
- New York University School of Medicine, NY, USA
Kenneth Rich
- New York University School of Medicine, NY, USA
Sindre Rolstad
- University of Goeteborg, Sweden
Lisa Mosconi
- New York University School of Medicine, NY, USA
Remigiusz Switalski
- New York University School of Medicine, NY, USA
Lidia Glodzik-Sobanska
- New York University School of Medicine, NY, USA
Susan De Santi
- New York University School of Medicine, NY, USA
Ray Zinkowski
- Applied Neurosolutions, Vernon Hills, IL, USA
Pankaj Mehta
- Institute for Basic Research, Staten Island, NY, USA
Domenico Pratico
- University of Pennsylvania, Philadelphia, PA, USA
Leslie A. Saint Louis
- New York University School of Medicine, NY, USA
Anders Wallin
- University of Goeteborg, Sweden
Kaj Blennow
- University of Goeteborg, Sweden
Mony J. de Leon
- New York University School of Medicine, NY, USA
- Nathan Kline Institute, Orangeburg, NY, USA
- Corresponding author at: Center for Brain Health, 550 First Avenue MHL-400, New York, NY 10016, USA. Tel.: +1 212 263 5805; fax: +1 212 263 3270.

Received 21 March 2007; received in revised form 13 July 2007; accepted 15 August 2007. published online 24 September 2007.

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-tau₂₃₁), amyloid beta (Aβ) Aβ₄₂/Aβ₄₀ ratio, isoprostane (IP) as well as P-tau₂₃₁/Aβ_42/40 and T-tau/Aβ_42/40 ratios.

Results

At baseline and at follow-up MCI-AD showed higher levels P-tau₂₃₁, T-tau, IP, P-tau₂₃₁/Aβ_42/40 and T-tau/Aβ_42/40 ratios and lower Aβ₄₂/Aβ₄₀ than MCI-MCI or NL-NL. Baseline P-tau₂₃₁ best predicted MCI-AD (80%, p<0.001) followed in accuracy by P-tau₂₃₁/Aβ_42/40 and T-tau/Aβ_42/40 ratios (both 75%, p's<0.001), T-tau (74%, p<0.001), Aβ₄₂/Aβ₄₀ (69%, p<0.01), and IP (68%, p<0.01). Only IP showed longitudinal effects (p<0.05).

Conclusions

P-tau₂₃₁ 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.

Keywords: Alzheimer's disease, Mild cognitive impairment, CSF biomarkers, Early detection, Longitudinal, Prediction