Biomarkers Consortium - Use of Targeted Multiplex Proteomic Strategies to Identify CSF-Based Biomarkers in Alzheimer’s Disease

The AD Targeted Cerebrospinal Fluid (CSF) Proteomics Project, completed in Q2Y15, was the second part of a multi-phased effort utilizing samples collected by the Alzheimer’s Disease Neuroimaging Initiative (ADNI), to qualify multiplex panels in both plasma and cerebrospinal fluid (CSF), with a goal of finding biomarkers for the diagnosis of patients with Alzheimer's disease (AD) and biomarkers to monitor disease progression. An earlier phase of the program focused on analysis of data from ADNI plasma samples run on a multiplex panel. This project leverages CSF samples from ADNI approved for use in assessing the utility of existing AD biomarker panels studies.

Goals

  • To validate a multiplex immunoassay panel as a tool to diagnose and monitor disease progression in the ADNI cohort, using CSF samples.
  • To examine Beta-Site APP Cleaving Enzyme (BACE-1) levels and enzymatic activity in CSF from the ADNI cohort.
  • To validate a Multiple Reaction Monitoring (MRM) mass spectrometry panel in the ADNI cohort, using CSF samples.

Results & Accomplishments

Results from the project have been uploaded to the ADNI LONI website and generated two published articles. In particular, this project allowed for the validation of a targeted proteomic multiplexed MS based approach.

Scientific Publications

Development and evaluation of a multiplexed mass spectrometry based assay for measuring candidate peptide biomarkers in Alzheimer's Disease Neuroimaging Initiative (ADNI) CSF. Spellman, D. S., Wildsmith, K. R., Honigberg, L. A., Tuefferd, M., Baker, D., Raghavan, N., Nairn, A. C., Croteau, P., Schirm, M., Allard, R., Lamontagne, J., Chelsky, D., Hoffmann, S., Potter, W. Z., Alzheimer's Disease Neuroimaging Initiative. Prot. Clin. Appl. 2015; 9:715-731

Soluble BACE-1 Activity and sAβPPβ Concentrations in Alzheimer’s Disease and Age-Matched Healthy Control Cerebrospinal Fluid from the Alzheimer’s Disease Neuroimaging Initiative-1 Baseline Cohort. Savage, M. J., Holder, D. J., Wu, G., Kaplow, J., Siuciak, J. A., Potter, W. Z. J. Alz. Dis. 2015; 46(2): 431-440

Data Access

ADNI LONI Website

Partners

Eisai Inc
Genentech, Inc.
Janssen L.P.
Eli Lilly and Company
Merck Sharp & Dohme Corp.
National Institute on Aging (NIA)
Pfizer Inc
Takeda Pharmaceuticals International, Inc.

Contact

Rosa Canet-Aviles, Scientific Program Manager, Neuroscience, rcanet-aviles@fnih.org