By Meghan McCarthy
The U.S. Census Bureau reports that 59.3% of the United States population are white individuals. Yet, a recent analysis of preclinical trials related to Alzheimer’s’ disease and related dementias (ADRDs) found that 85.9% of the 59,455 research participants involved where white.
ADRDs disproportionally impact ethnic minorities, and researchers around the country are working to understand why.
Historically, African Americans, Hispanic, and Asian Americans are substantially underrepresented in AD research populations. The Alzheimer’s Disease Sequencing Project (ADSP), which uses multi-ancestry study groups, aims to bridge this gap.
“We know the problem and have to do the work,” said Li-San Wang, PhD, a leader of the Penn Alzheimer’s Disease Research Center and co-director of the Penn Neurodegeneration Genomics Center.
Research has demonstrated a clear relationship between Alzheimer’s disease and related dementias (ADRDs) and underlying genetic causes. However, genetic factors that can be detected in early disease stages and apply to diverse populations remains widely unknown.
Dr. Wang strives to do this through the ADSP. He serves as director of the NIA Genetics of Alzheimer’s Disease Data Storing Site (NIAGADS), which is the coordinating center for ADSP.
The project aims to identify new genes involved in AD, gene alleles which contribute to increase risk for or protection against AD, and provide insight to new therapies in disease prevention.
Since its launch, ADSP has sequenced more than 36,000 genomes.
Gene sequencing uses a biological sample (like blood or saliva) to determine the order of nucleotides within DNA. Nucleotides are the code that comprises your genetic makeup. The order, or sequence, of the code, changes how genes are expressed. A genome is the complete sequence of DNA code within an individual.
Small changes in the code, known as variants, can cause diseases such as ADRDs.
“We analyze the entire genome,” said Dr. Wang. “We are looking at rare variants or mutations that despite being rare, probably have a strong effect – such as increasing risk by twofold.”
While variants may not contribute to risk of ADRDs in an entire population, they provide helpful insight to targeting ADRD in early stages.
ADSP strives to understand how the genetics of ADRDs vary across diverse populations.
For example, the effect of a mutation may depend on an individual’s ethnic background. For example, one variant, known as APOE e4, increases the risk of AD in patients by:
- 3.4-fold in Europeans
- 2.3-fold in Africans
- 5-fold in Asians
“We need well-characterized samples from minority populations,” said Dr. Wang. “Over half of the sample comes from minority populations. It’s incredibly exciting.”
In his work, Dr. Wang leads a focused sequencing effort for the Asian population called the Asian Cohort for Alzheimer’s Disease (ACAD).
Asian-American and Pacific Islander (AAPI) communities pose unique challenges for research recruitment. For example, many research institutions aren’t located in proximity to AAPI cities. Communities also have many languages and dialects.
To combat this, Dr. Wang and the ACAD team, which consists of Principal Investigators (PIs) and staff from more than 10 academic institutions across US and Canada, utilizes community-based participatory research practices, which includes a community advisory board that provides input on translation and cultural awareness.
“For big research operations such as these, it takes time to build a connection and trust with the community,” said Dr. Wang. “A lot of people need to work together to solve all of these problems together.”
The ACAD team plans to recruit 5,000 participants of Chinese, Korean, and Vietnamese ancestry in the US and Canada.
One of Dr. Wang’s primary goals includes developing a disease risk model that provides sensitive diagnosis for the AAPI population.
“There are a lot of young investigators who are the future of Alzheimer’s research in American for the Asian population,” said Dr. Wang. “They are committed to the cause and a much-needed next generation.”