Aiming to shine a brighter light on a relatively underexplored area of Alzheimer’s research, ATRI is intensifying its research efforts on Down syndrome-related Alzheimer's disease (DS-AD). Under the guidance of ATRI Medical Director Michael S. Rafii, MD, PhD, the work will delve into the staggeringly high prevalence of Alzheimer's in the Down syndrome population.
Jason Russell, PhD, a new postdoctoral research assistant, will play a crucial role in this initiative. His primary focus will be on advancing our understanding of DS-AD, a field that has only recently come under increased attention. Dr. Russell has been closely collaborating with Dr. Rafii for the past several years. He joins ATRI from Vanderbilt University Medical Center, where he served as a postdoc fellow.
“This is a population that is at very high risk of developing Alzheimer’s disease, that until recently has really been overlooked,” Dr. Russell said of individuals with Down Syndrome. “I think that’s an issue, and that is something that I want to do my part to help change.”
What Do We Know about Alzheimer’s Disease in Those with Down Syndrome?
Up to nine in 10 people with Down syndrome go on to develop Alzheimer’s disease as they age. Alzheimer’s disease occurs when amyloid plaques build in the brain. In people with Down syndrome, these plaques are caused by an extra chromosomal gene that then triggers production of the protein beta-amyloid which causes the plaques. Most individuals with Down syndrome start to form these plaques by age 40, making Alzheimer’s the number one cause of death in adults with Down syndrome.
While based at Vanderbilt, Russell contributed to the ATRI-led research study Trial-Ready Cohort-Down Syndrome (TRC-DS). This critical study is developing a group of eligible participants with Down syndrome who can participate in future Alzheimer’s disease-related clinical trials. It is part of the even larger Alzheimer’s Clinical Trials Consortium – Down Syndrome (ACTC-DS), an NIH-funded consortium also led by ATRI. ACTC-DS collaborates across multiple U.S. and international sites to conduct research and clinical trials with the goal of advancing Alzheimer’s disease therapies for those with Down syndrome.
Surprising Recent Findings
A recent study led by Dr. Russell, who is a native of England and a graduate of the University of Cambridge, made some unexpected findings on the differences between adults with and without Down syndrome. The results of the study were featured in the article, “Differences in cholinergic terminal density in adults with Down syndrome compared to neurotypical controls measured by [18F]-fluoroethoxybenzovesamicol positron emission tomography imaging - ScienceDirect,” published in Neurobiology of Aging. The study found that participants with Down syndrome showed a much higher level of a cholinergic system marker compared to those without Down syndrome. The cholinergic system is one of the earliest neurological systems to be affected in the brain by Alzheimer’s disease. It plays an important role in memory, learning and attention, among other functions.
“We weren’t expecting to see much difference if any,” Dr. Russell said of the cholinergic markers in those with and without Down syndrome. “But we saw a profound difference.”
Those with Down syndrome then showed a much greater reduction in cholinergic markers with increasing age than was observed in those without Down syndrome.
Dr. Russell and his co-authors, including Dr. Rafii, are not sure why yet, though they have a working hypothesis. This is one of many related questions that the team at ATRI is eager to continue to study.
The study was also the first ever to look at the cholinergic system in people with Down syndrome using PET scans. Previously, researchers had used other methods to conduct research in this area. PET imaging uses tracers to provide detailed images of activity within the body.
Russell and ATRI’s Plan of Attack
Dr. Russell will strengthen ATRI’s team when it comes to expertise in neuroimaging, including tests such as MRI and PET imaging. Russell will dive into data collected over the past decade from studies led by ATRI and fellow research organizations. He will focus on looking at the brain’s neurological activity and structures and how they change as Alzheimer’s disease develops in people with Down syndrome. He and the team will also look at how these changes affect thinking and memory. Within ATRI, he will closely collaborate with the Biomarker Laboratory and Biorepository, which is led by Robert Rissman, PhD. He will also work with Zinayida Schlachetzki, MD, PhD, another ATRI researcher studying Alzheimer’s disease in people with Down syndrome.
The aim is to gain a more precise understanding of where medicine can intervene to prevent the progression of Alzheimer’s disease in those with Down syndrome. The findings could be used to help design clinical trials that benefit those with Down syndrome.
“We are thrilled to welcome Dr. Russell to ATRI and leverage his neuroimaging expertise to enhance our understanding of Down syndrome-related Alzheimer's disease,” said Dr. Rafii. “These are exciting times in the field, and his work will significantly advance our efforts.”