Exposing the Brain Proteomic Signatures of Alzheimer’s Disease in Diverse Racial Groups: Leveraging Multiple Datasets and Machine Learning

Recent studies have highlighted that the proteome can be used to identify potential biomarker candidates for Alzheimer’s disease (AD) in diverse cohorts. Furthermore, the racial and ethnic background of participants is an important factor to consider to ensure the effectiveness of potential biomarkers for representative populations. A promising approach to survey potential biomarker candidates for diagnosing AD in diverse cohorts is the application of machine learning to proteomics datasets. Herein, we leveraged six existing bottom-up proteomics datasets, which included non-Hispanic White, African American/Black, and Hispanic participants, to study protein changes in AD and cognitively unimpaired participants. Machine learning models were applied to these datasets and resulted in the identification of amyloid-β precursor protein (APP) and heat shock protein β-1 (HSPB1) as two proteins that have high ability to distinguish AD; however, each protein’s performance varied based upon the racial and ethnic background of the participants. HSPB1 particularly was helpful for generating high areas under the curve (AUCs) for African American/Black participants. Overall, HSPB1 improved the performance of the machine learning models when combined with APP and/or participant age, and it is a potential candidate that should be further explored in AD biomarker discovery efforts.