Biomarkers Consortium - Use of Targeted Multiplex Proteomic Strategies to Identify CSF-Based Biomarkers in Alzheimer’s Disease
Revolutionizing the ability to diagnose early-stage Alzheimer’s disease, and enabling earlier and more effective treatments for patients
The AD Targeted Cerebrospinal Fluid (CSF) Proteomics Project, completed in 2015 as the second stage of a multi-phased effort, used samples from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to qualify multiplex panels in cerebrospinal fluid (CSF), aiming to identify biomarkers for diagnosis of Alzheimer’s disease (AD) and monitoring of their disease progression. This project leveraged ADNI CSF samples that were approved for use in assessing the utility of AD biomarker panels. Data are now publicly available via the University of Southern California’s Laboratory of Neuroimaging (LONI).
- 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 as a diagnostic biomarker of AD dementia.
- To validate a Multiple Reaction Monitoring (MRM) mass spectrometry panel in the ADNI cohort, using CSF samples.
National Institute on Aging (NIA)
Eisai Inc Genentech, Inc. Janssen L.P. Eli Lilly and Company Merck Sharp & Dohme Corp. Pfizer Inc Takeda Pharmaceuticals International, Inc.
Wesley Horton, M.S., Scientific Project Manager, Neuroscience; firstname.lastname@example.org
Results & Accomplishments
Data and Publications
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 mass spectrometry-based assay for the qualification of candidate AD biomarkers. Several peptides were identified as potential diagnostic or prognostic (predicting progression from MCI to AD) markers. Further study results demonstrated that there is no diagnostic utility of CSF BACE-1 enzymatic activity and concentration to differentiate among healthy elderly, mild cognitively impaired and AD individuals.
- 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