Exploring Genetic Variants and Global Challenges in Alzheimer Disease Research: Jeffery M. Vance, MD, PhD

WATCH TIME: 10 minutes

"Alzheimer is a global disease, not just something that affects poor people; it affects everyone, and we need to address it in that manner."

The Alzheimer’s Disease Sequencing Project (ADSP) is an initiative by the National Institute on Aging focused on identifying genetic variants that either increase the risk of or provide protection against Alzheimer disease (AD). In its current phase, the study concentrates on whole genome sequencing in non-European populations, including Hispanic/Latino, non-Hispanic Black individuals with African ancestry, and Asian groups. At the 2024 Alzheimer’s Association International Conference, held from July 28 to August 1, in Philadelphia, Pennsylvania, a recent study provided an overview of the clinical characteristics within the ADSP cohorts.¹

Presented by coauthor Jeffery M. Vance, MD, PhD, and his team, the ADSP now includes 40 cohorts totaling approximately 36,300 participants. Researchers plan to sequence over 110,000 individuals from diverse racial and ethnic backgrounds. To date, genotyping, sequencing, and clinical adjudication have been completed for 36,361 participants. The mean ages of cases and controls across cohorts ranged from 57.0 to 86.5 years for cases, and 63.3 to 90.0 years for controls. Women made up about 61% of the participants, with 60.3% in the case group, 63.7% in the cognitively unimpaired group, and 55.8% in the AD and related dementia group. Additionally, the highest frequency of APOE ε4/ε4 carriers was found among non-Hispanic white patients (7.4%), while the lowest frequency was observed in Asian participants (1.7%).

At the conference, Vance also gave a symposium presentation titled "Accelerating Therapeutic Development: A Global Commitment by the Alzheimer's Disease Sequencing Project”. In an interview during the meeting, Vance, the director of the Center for Genomic Medicine at the Miami Institute for Human Genomics, sat down with NeurologyLive^® to discuss how different APOE variants influence AD risk, and potential therapies that are being explored based on these findings. Deeper into the conversation, Vance, who also serves as a professor in the Department of Human Genetics and Neurology at the University of Miami Miller School of Medicine, talked about challenges that researchers face in developing treatments that are effective across diverse global populations. Moreover, he spoke about how the high cost of emerging AD treatments can potentially be managed to ensure accessibility, especially in low- and middle-income countries.

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REFERENCES
1. Leverenz JB, Patel P, Bekris LM, et al. Synuclein Aggregate Assay Performance in Autopsy-Confirmed Lewy Body Dementia: Results from the U.S. Dementia with Lewy Bodies Consortium. Presented at: 2024 Alzheimer’s Association International Conference; July 18 to August 1; Philadelphia, Pennsylvania.