Identification of a novel panel of cerebrospinal fluid biomarkers for Alzheimer's disease

Simonsen, A.H.; McGuire, J.; Podust, V.N.; Davies, H.; Minthon, L.; Skoog, I.; Andreasen, N.; Wallin, A.; Waldemar, G.; Blennow, K.

doi:10.1016/j.neurobiolaging.2007.01.011

« Previous Next »Neurobiology of Aging
Volume 29, Issue 7 , Pages 961-968, July 2008

Identification of a novel panel of cerebrospinal fluid biomarkers for Alzheimer's disease

A.H. Simonsen
- Biomarker Discovery Center^® Facility, Ciphergen Biosystems Inc., Copenhagen, Denmark
- Memory Disorders Research Group, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark
- Corresponding author at: Ciphergen Biosystems, Symbion Suite 253, Fruebjergvej 3, 2100 Copenhagen O, Denmark. Tel.: +45 3917 9748; fax: +45 3917 9742.
J. McGuire
- Biomarker Discovery Center^® Facility, Ciphergen Biosystems Inc., Copenhagen, Denmark
V.N. Podust
- Biomarker Discovery Center^® Facility, Ciphergen Biosystems Inc., Fremont, CA, USA
H. Davies
- Biomarker Discovery Center^® Facility, Ciphergen Biosystems Inc., Copenhagen, Denmark
L. Minthon
- Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden
I. Skoog
- Department of Neuroscience and Physiology, Sahlgren's University Hospital, Sweden
N. Andreasen
- Department of Geriatric Medicine, Karolinska Institute, Karolinska University Hospital, Huddinge, Sweden
A. Wallin
- Department of Geriatric Medicine, Karolinska Institute, Karolinska University Hospital, Huddinge, Sweden
G. Waldemar
- Memory Disorders Research Group, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark
K. Blennow
- Department of Clinical Neuroscience, Sahlgrenska University Hospital, Mölndal, Sweden

Received 15 September 2006; received in revised form 17 January 2007; accepted 21 January 2007. published online 26 February 2007.

Abstract

An early and accurate diagnosis of Alzheimer's disease (AD) is required to initiate symptomatic treatment with currently approved drugs and will be of even greater importance if disease modifying compounds in development display a clinical effect.

Protein profiles of human cerebrospinal fluid samples from AD patients (n=95) and population-based healthy controls (n=72) were analyzed by SELDI-TOF-MS in order to discover and characterize novel candidate biomarker combinations that differentiate AD patients from normal aging in this explorative study.

Thirty candidate biomarkers (ROC AUC>0.7) were discovered that could differentiate patients with AD from healthy controls. Protein sequence determination and positive identification of 15 biomarkers revealed potential associations between the identified markers and AD pathogenesis. A multi-marker combination of five peaks could distinguish AD from healthy control individuals with high sensitivity (97%) and specificity (98%). The panel of five markers was tested on a blinded independent data set of 30 AD samples and 28 controls giving 100% sensitivity and 97% specificity.

This novel panel of biomarkers could potentially be used to improve the accuracy of diagnosis of AD.

Keywords: Alzheimer's disease, Biomarkers, SELDI, Proteomics, CSF