International Brain Bank for Down Syndrome-Related Alzheimer’s Disease
The focus of this special project is to develop a strong collaborate network between six different research groups focused on providing much-needed information about the Down syndrome population, of which as many as 80 percent have Alzheimer’s pathology by the time they are in their 50s and 60s. Although there are many centers and researchers that focus on Alzheimer’s in the general population, few of them focus on people with Down syndrome. The information generated by our project will be of great help to those with Down syndrome and those with Alzheimer’s disease.
The long-term goal of this project is to determine the neurobiological mechanisms underlying the onset of Alzheimer's disease (AD) type dementia in Down syndrome (DS).
The first aim of this project is to bank high quality biological research samples, linked to clinical data, from both national and international cohorts of people with DS and dementia, and develop an internationally accepted neuropathological staging protocol for this vulnerable population.
The second goal is to make these samples available to facilitate collaborative research projects into the neurobiological mechanisms of DS-related AD that may also be translatable to the general AD population.
The third goal is to perform collaborative research studies into the early events underlying dementia in people with intellectual disabilities with many different research groups in the USA and Europe, with the specific purpose of developing new therapeutic targets for people with DS and dementia, which may translate to those with AD and other dementias in the general population.
This project is unique in that it is the only funded biobank consortium in the United States focused on people with intellectual disabilities. The life span of this population has increased over the last few decades, and age is a major factor associated with Alzheimer’s dementia. Few studies have focused on this medically under-investigated group.
About the Researcher
All investigators involved in this project have significant experience in the Down syndrome and Alzheimer fields.
Ann-Charlotte Granholm, PhD, DDS, is the executive director of the Knoebel Institute for Healthy Aging at University of Denver (DU). She has a broad background in neurodegenerative disease, especially as it pertains to Down syndrome (DS), Alzheimer’s disease (AD) and aging. She has been funded by the NIH for 25 years and has more than 160 peer-reviewed articles, most of them related to aging, neurodegeneration, or behavioral alterations associated with aging, including both cognitive and motor domains of function. Dr. Granholm was the director of the Brain Bank at the Medical University of South Carolina (MUSC) for 15 years, and is now the inaugural Executive Director for the Knoebel Institute for Healthy Aging at DU since 2016. Dr. Granholm’s laboratory is highly focused on exosome work, both in mouse models and humans. Dr. Granholm recently published the first study on AD biomarkers in exosomes from patients with DS-related AD and controls, demonstrating that AD biomarkers are present early in life in those with DS. This was a collaborative study, co-authored by Dr. Mufson (below) and several collaborative partners.
Elliott Mufson, PhD, is professor of Neurobiology and director of the Alzheimer’s Research Laboratory at the Barrow Neurological Institute in Phoenix, AZ. He is the principal investigator of a multisite clinical molecular neuropathology program project grant entitled “Neurobiology of Mild Cognitive Impairment in the Elderly,” supported by the National Institute of Aging. This program involves investigators at several different universities and Alzheimer disease (AD) centers within the USA. He brings to the project his research perspective in human brain clinical pathological studies, as well as expertise in human single cell gene array technology. He is an internationally recognized expert in human brain connectivity and the neurobiology of mild cognitive dementia and AD and has published over 300 peer-reviewed publications on molecular and cellular pathology of AD and DS in human brain and mouse models of this disorder.
Elizabeth Head, PhD, directs the University of Kentucky Aging Study in Down Syndrome, consisting of a cohort of more than 70 adults with DS, a cohort made up primarily of individuals without dementia, as well as a smaller group of individuals with dementia who have been followed for up to eight years. This study has been funded by the NIH/NICHD (R01HD064993). Dr. Head has published extensively in the DS, aging, and dementia field, with over 50 papers in this area. She has contributed to several books and special topics issues dedicated to describing research in aging adults with DS. She brings her expertise in lifespan changes in brain proteins that may contribute to AD (AD) in DS. Her current work is focused on cerebrovascular dysfunction and white matter integrity losses as underlying pathologies contributing to the development of dementia in DS. Dr. Head has a background of working on autopsy tissue from DS donors, having served as co-leader of the University of California-Irvine AD Research Center Neuropathology Core, and director of its brain Tissue Repository. She also has been involved with imaging studies in DS to detect structural, connectivity and cerebrovascular changes as a function of age and dementia.
I became involved in this research field in the early 1990s, working on aging effects in people with intellectual disabilities, and using mouse models for Down syndrome. I quickly realized that this field was an unusually friendly one; I think the overall positive and altruistic demeanor of the population with Down syndrome rubbed off on the often passionate and highly involved researchers in this field. For a long time, we have been discouraged by the lack of federal funds to study aging processes in people with intellectual disabilities. We are therefore so grateful to BrightFocus Foundation and its donors for the opportunity to finally form this important consortium of people in the USA and in Europe (Barcelona) to focus on studying the Alzheimer pathway in people with Down syndrome.
Martini AC, Helman AM, McCarty KL, Lott IT, Doran E, Schmitt FA, Head E. Distribution of microglial phenotypes as a function of age and Alzheimer's disease neuropathology in the brains of people with Down syndrome. Alzheimers Dement (Amst). 2020 Oct 14;12(1):e12113. doi: 10.1002/dad2.12113. PMID: 33088896; PMCID: PMC7560512 p>
First published on: June 8, 2018
Last modified on: November 12, 2020