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Fields & Applications Clinical, Metabolomics & Lipidomics

Alzheimer’s Disease: Inclusion Matters

Can you tell me a bit about the work you’ve been doing within the Alzheimer’s space since we last spoke?

Over the last few months we’ve really been advancing our efforts to use proteomics and lipidomics for testing biospecimens from representative samples of under-represented groups – mostly African American and Black adults. Our recent work kicked off with a pilot paper we published that looks at postmortem brain tissue from a small cohort of African Americans and non-Hispanic whites. The aim was to determine whether we could see any differences in protein biomarkers when we stratified based on how individuals self-reported their race. This gave us the initial insight that there might be some significant differences in the proteome between people from different ethnic groups, but it also highlighted that a majority of pathways seem pretty consistent regardless of who presents with Alzheimer’s disease.

How did this project lead to your plasma biomarker research?

After the initial work to understand the importance of self-reported race, we decided to focus on plasma biomarkers and look at a larger cohort. There were two aims to this research: one, to see whether plasma biomarkers could be used to diagnose individuals already clinically confirmed to have AD or probable AD; and two, to see how those biomarkers already selected as “good candidates” fared when you tested them against the patients in our cohort study of non-Hispanic whites and African Americans. This involved a collaboration with Heather Desaire and Mostafa Khan, who applied machine learning approaches to our analysis of the plasma proteomics of AD. The outcome was that, if you looked at everyone across ethnic groups, these biomarkers performed pretty well overall. But if you started looking at specific ethnic groups, the algorithms clearly showed better outcomes for the non-Hispanic white groups. Interestingly, we evaluated how including certain parameters such as genetic (APOE4) status, age, sex, and education improved performance outcomes for non-Hispanic whites or African Americans.

What the previous study told us is that it’s not only crucial to include a wide range of individuals in this research to fully understand which proteins make good biomarker candidates, but also to look at other measures we should be including in these biomarker studies. By this, I mean other variables that might have an impact on study results, such as quality of education, lived experiences, and genetic biomarkers.

You’re looking at the lipidomics behind AD, too?

Yes – everything we’re doing with proteins, we’re also (broadly) trying to understand in the context of lipids. So we took the same set of patients from the plasma biomarker study and did a targeted lipidomics analysis. That work is actually very interesting because the data are so clear – when you look at 1,100 different lipid markers, they can very easily be used to distinguish AD across populations. However, if you stratify them based on race, it shows that non-Hispanic whites and African Americans with AD in our study were distinguishable. The cognitively unimpaired individuals were more similar regardless of race.

What are the next steps for your research?

We are now equipping ourselves to handle larger numbers of samples from studies with a significant representation of African American adults. We also have collaborators who are sharing samples from Hispanic and Latinx adults, as well as non-Hispanic whites. The core driver behind this is an NIH grant that was funded to enable us to study hypertension as a risk factor for AD and to examine how biochemical markers can be used to evaluate that risk.

What’s the biggest takeaway from this research?

The biggest thing we’ve learned from these studies is that you absolutely have to look at a lot of people across diverse ethnic groups. A lot of what we know about disease has come from a European-centric, non-Hispanic white cohort. Before we can even generalize within the African American community, we need a broader set of individuals to partake in these studies to ensure they are as representative as possible. This doesn’t just benefit African Americans; it benefits us all by ensuring we better understand the disease as a whole. The work that needs to be done now is understanding how this fits into all the other social, behavioral, and lived experiences that contribute to these molecular disparities. Our work is just one piece in this entirely complicated puzzle of why disparities exist to begin with.

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