The level of diversity that exists globally has not been documented in large-scale clinical trials for Alzheimer’s disease (AD). This under-represesentation limits our understanding of disease progression and exacerbates health inequalities, especially in light of the fact that many populations that are understudied in AD research are at increased risk of disease.
94.7 percent. A recent investigation digging into the percentage of White participants in clinical trials for Alzhiemer’s disease found that in 101 studies profiled between 2001 and 2019, the average percentage of White participants was 94.7%.
African Americans are 1.4 times more likely than European Americans to carry the apolipoprotein E (APOE) ε4 risk factor for AD. Despite this increased risk, studies tracking the neural correlates of cognitive decline and disease progression in African Americans have been limited. Efforts including the Healthy Aging in Neighborhoods of Diversity across the Life Span cohort study (https://clinicaltrials.gov/ct2/show/NCT01323322) have provided crucial insights between the relationships between race, APOE genotype, and cognition; however, these studies often recruit a limited number of participants and require additional funding, attention, and recruitment.
Take for example the events that happen in African Americans with progressive chronic and end stage kidney disease. There are two African-specific risk variants (i.e. changes) in a gene called APOL1 that lead to a 7- to 10-fold increased risk for kidney disease. It is studies like this one that highlight why African Americans have a higher incidence of end stage kidney disease than European Americans. Of interest, these variants occur at higher frequency in individuals of West African descent because they are protective against sleeping sickness caused by an insidious protozoa. What other clues into the origin of disease are we missing by not taking into account the local adaptations in the genetic architecture of complex diseases?
The National Human Genome Research Institute catalogs the results of genome wide association studies with the goal of using genetic evidence to enhance the success of drug target identification. The question remains: drug target identification for which patient populations? In a call to arms to increase diversity in clinical trials published in the prestigious journal Cell in 2019, researchers from the University of Pennsylvania reported that the number of individuals included in GWAS studies based on ethnicity has the following ancestry distributions: 78% European, 10% Asian, 2% African, 1% Hispanic, and all other ethnicities represent < 1% of GWAS (https://www.ebi.ac.uk/gwas/home).
Genetic variation among diverse populations can affect how likely a drug will work and also how likely it might be to cause adverse side-effects.
What can the Alzheimer’s disease research field learn from cancer research? The Count Me In project, for example, successfully accomplished the goal of generating a database of patient-reported data with the possibility of providing a benefit for every person affected by cancer, especially individuals from marginalized communities who have historically been excluded from research, no matter whether they live close to a major research institution. The success of Count Me In depends on patients across all backgrounds and experiences being able to share saliva samples, medical records, and survey responses without leaving home. The data is then de-identified and shared with researchers all over the world to accelerate progress against all forms of cancer.
The Alzheimer’s disease research community has its own grassroots, patient-driven efforts to learn more about disease progression in the form of the Brain Donor Project. The Brain Donor Project’s core mission is the following: to increase the recruitment of underrepresented Americans for brain donation registration.
Built on the legacy of Gene Armentrout who understood that his brain could be valuable for other patients who also suffered from Lewy Bodies Dementia, the Brain Donor Project seeks to increase brain donation for research by connecting patients to the NeuroBio Bank, part of the National Institute of Health. Importantly, the BDP understands that science benefits when patients from every background are included and is seeking to bridge the knowledge gap by partnering with patients from every community. The research community is seeking to remedy exclusionary practices of the past by including minority populations in biobank initiatives. The BDP encourages donations of healthy brains (for controls) and also those with neurologic disorders, and more information can be found on their website: braindonorproject.org. The Brain Donor Project states their mission best: you can be the brain behind the breakthrough.