Proteomics and Lipidomics to Study Racial Disparities in Alzheimer’s Disease

Abstract

Racial disparities in Alzheimer’s disease (AD) is less recognized, specifically among African American/Black adults. Primary manifestations of AD are similar for everyone irrespective of race when considering Aβ plaques and tau tangles, although recent evidence indicates racial differences in the levels of AD biomarkers (e.g. cerebrospinal fluid total-tau and phosphorylated tau protein). A primary consideration is that comorbidities such as high cholesterol, vascular disease and hypertension, are also prevalent in African Americans. Studies involving African American/Black adults in AD have been limited and little is known about the differences in AD pathogenesis among African American/Black adults compared to non-Hispanic Whites. Omics’ approaches such as proteomics and lipidomics have the capability to comprehensively analyze the overall proteome or lipidome to discover potential changes in disease pathology due to disease or race. In this body of work, we have employed proteomics and lipidomics techniques to understand the molecular factors that might be responsible for health disparities in AD. To achieve this goal, we first established a robust proteomics workflow for studying human plasma, and applied it to plasma samples obtained from cognitively normal and AD individuals of both African American/Black and non-Hispanic White backgrounds to identify changes in the proteome due to AD that are race specific. We combined the proteomics results with machine learning to propose potential diagnostic biomarkers in AD. Next, in order to establish a robust and reproducible lipidomics workflow for plasma, we compared and contrasted an untargeted against a targeted mass spectrometry approach to study changes in the lipidome due to AD in a pilot study. Later, we applied the developed approach and applied it to the same cohort as the proteomics analysis, to discover potential lipid changes specific to race and disease. This is the first application of omics’ approaches in plasma to study racial disparities in AD, and these studies have provided emphasis on the need for more studies involving African American/Black and other minority groups in AD.