Developing a Robust Biomarker Discovery Proteomics in Alzheimer's disease (AD)
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1
Vanderbilt University, United States
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder, which leads to 60-70% of cases of dementia. Currently, there is an urgent need for noninvasive and specific clinical biomarkers that can be used for disease diagnosis at different disease stages. Additionally, these biomarkers need to be applicable to subpopulations of AD patients, including those that come from racially disparate populations. Proteomics is a powerful tool that has been widely employed in the discovery of biomarkers in many diseases as it allows rapid identification and quantification of proteins. The long-term goal of this work is to generate a comprehensive proteomics workflow to identify potential biomarker candidates for AD across various biofluids [cerebrospinal fluid (CSF), serum, and plasma] that will be tested across a diverse group of AD patients and cognitively normal individuals. To this end, this poster will focus on the development of targeted MS assays based from discovery based assays on two high-resolution Orbitrap instruments: the Q Exactive HF and Fusion Lumos MS.
For the discovery phase of this project, quality control (QC) serum or CSF samples from AD and cognitively normal individuals are subject to typical shotgun proteomics approach. Optimized conditions for sample preparation, sample clean-up, trypsin digestion, LC-MS conditions (DDA, topN MS/MS, DE) will be developed using the Fusion Lumos platform. From these experiments, we then apply the optimized platform to a small cohort of clinical samples from individuals of different ethnic backgrounds. The proteins that are found to be significantly differentially expressed by disease and ethnic background are then used to generate a parallel reaction monitoring (PRM) list for the targeted phase of the project. The PRM experiments are performed on the Q Exactive HF platform. Preliminary data on the analytical performance of both phases of this project and initial findings of potential biomarker candidates will be presented.
Keywords:
Alzheimer’s disease (AD),
Biomarkers,
proteomics,
LC-MS,
neurodegenerative
Conference:
National Organization for the Professional Advancement of Black Chemists and Chemical Engineers (NOBCChE) 45th Annual Conference , Orlando, Florida, United States, 17 Sep - 20 Sep, 2018.
Presentation Type:
Poster Presentation
Topic:
Analytical Chemsitry
Citation:
Goyal
S,
Dunham
WC,
Stepler
KE,
Khan
M and
Robinson
RA
(2019). Developing a Robust Biomarker Discovery Proteomics in Alzheimer's disease (AD).
Front. Chem.
Conference Abstract:
National Organization for the Professional Advancement of Black Chemists and Chemical Engineers (NOBCChE) 45th Annual Conference .
doi: 10.3389/conf.fchem.2018.01.00026
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Received:
15 Oct 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Prof. Renã A Robinson, Vanderbilt University, Nashville, United States, rena.as.robinson@vanderbilt.edu