Expanding the Alzheimer Disease Sequencing Project for Diverse Therapeutic Targets: Jeffery M. Vance, MD, PhD

WATCH TIME: 10 minutes

"Different ancestries have different risks and different causes for Alzheimer which are very important [to understand], and this is coming out of the [Alzheimer's Disease Sequencing Project]."

The Alzheimer's Disease Sequencing Project (ADSP) is a National Institute on Aging-sponsored initiative centered on identifying genetic risk and protective variants in patients with Alzheimer Disease (AD). The current phase of the study is focused on whole genome sequencing of non-European populations including Hispanic/Latino, non-Hispanic Black with African Ancestry, and Asian populations. In a recent study presented at the 2024 Alzheimer’s Association International Conference, July 28 to August 1, in Philadelphia, Pennsylvania, the results provided an overview of clinical features in ADSP cohorts.¹

Presented by coauthor Jeffery M. Vance, MD, PhD, and colleagues, the ADSP currently consists of 40 cohorts comprised of approximately 36,300 patients, with researchers planning to sequence over 110,000 participants from diverse race/ethnicity. As of now, genotyping, sequencing, and clinical adjudication was performed on 36,361 patients. Mean ages for cases and controls varied across cohorts, 57.0 to 86.5 cases and 63.3 to 90.0 controls. About 61% participants were women and distributed as the following: cases (60.3%), cognitively-unimpaired (63.7%), and AD and related dementia (55.8%). Furthermore, the highest for APOE ε4/ε4 carriers were observed in non-Hispanic whites patients (7.4%) and the lowest in Asians (1.7%).

During the conference, Vance also gave a presentation on "Accelerating Therapeutic Development: A Global Commitment by the Alzheimer's Disease Sequencing Project” in a symposium. In an interview, Vance, the director of the Center for Genomic Medicine at the Miami Institute for Human Genomics, sat down with NeurologyLive^® to discuss how the ADSP aims to address the genetic diversity in AD research. Further into the conversation, Vance, who also serves a professor in department of human genetics and neurology at the University of Miami Miller School of Medicine, talked about the role of ancestry-specific factors play in the development and progression of AD according to ADSP findings. Additionally, he spoke about how the ADSP incorporates social determinants of health in its research, and its importance.

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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.