CADRE is focused on rapidly expanding the scientific community’s understanding of the genetic architecture of Alzheimer’s Disease (AD) and related dementias. This work has a particular emphasis on populations that historically have not been represented in large scale genetic research.
Many of our investigators have played roles in national and international research consortia, defining the Alzheimer’s Disease genetic research agenda over many decades. Our group members represent institutions that are founding members of the Alzheimer’s Disease Sequencing Project, with data that will be included in this effort.
In the genetics research arena – five years – is a rapid timeline for research on this scale. Teams are working in tandem, building on findings and genetic relationships previously uncovered to move as quickly as possible toward identifying targets for treatment and prevention.
Massive Data Sets
We are drawing on existing data collections from around the world, and generating new data in collaboration with communities historically not represented in large scale genetic research. Our projects are inclusive of communities with Caribbean, African, Hispanic, and Indigneous heritage.
Our Motivation and Approach
Alzheimer’s Disease and related dementias are the most common neurodegenerative disease in the US, affecting more than 35% of people aged 85 and older. To date, there is no cure, and currently available drugs have only a marginal and temporary effect on disease progression and severity.
Members of the CADRE team have dedicated their careers to finding the genetic underpinnings of Alzheimer’s Disease and other dementias, along with other conditions related to aging.
All of us know the devastating consequences of this disease and feel a pressing need to accelerate the work. Through the CADRE initiative, we are building on the last three decades of research by applying analysis techniques we have developed to assess massive genomic data sets. This scale will advance our efforts to identify additional genetic variants, how they interact with defined variants, and how they all correlate to disease – or offer protection from disease – as well as the proteins and biological mechanisms they influence.
Our ultimate goal is to identify targets for effective treatments or prevention.
Nearly 30 years ago, the first key genetic risk factors for Alzheimer’s Disease were discovered through analyses of affected families. Since then, multiple additional genetic variants have been discovered, but the majority of these studies have been conducted with non-Hispanic white individuals. We are just beginning to understand how genetic risk for the disease changes for individuals with different ancestry and heritage. For example, we know that a key genetic risk factor identified in non-Hispanic whites – APOE – correlates to lower risk in populations with African ancestry.
The CADRE team will expand our understanding of the genetic basis of Alzheimer’s Disease and related dementias, with a commitment to including populations that historically have been underrepresented in large-scale genetic research.
The CADRE group is focused on analyzing genomic sequence data from the Alzheimer’s Disease Sequencing Project (ADSP) to identify the highest priority genetic variants and mechanisms that may be potential therapeutic targets.
Key aspects of the work include:
- Characterizing genomic variation in people with Alzheimer’s disease (AD) from ethnically diverse data sets
- Using admixture analyses to understand how ethnic ancestry influences the genomics of AD
- Compiling results and making them available to the nationwide AD research community
- Prioritizing disease genes and mechanisms that may be influenced by new or existing therapeutics based on our existing knowledge about AD development
Updates and Publications
As we report out on our grant AIMS and have published papers to share, we will post them on our publications page.
Funding for this work is through the NIH’s National Institute on Aging
- Grant number: 1U01AG058654-01A1 / THE ALZHEIMER DISEASE SEQUENCE ANALYSIS COLLABORATIVE
- The grant is administrated through the Department of Population and Quantitative Health Sciences at Case Western Reserve University School of Medicine.