Can identifying changes in the genetic material inform the biological mechanisms of Alzheimer’s progression?
Jaroslav Bendl, Ph.D.
Icahn School of Medicine at Mount Sinai
New York, NY - United States
Researchers believe that there is not a single cause of Alzheimer’s, but rather it develops over time as a result of multiple factors such as lifestyle, environment, and genetics. In addition to studying specific genes that increase risk, researchers would also investigate biological mechanisms by which genes can be modified or activated. For example, researchers use epigenome or transcriptome to study the biological mechanisms by which genes may be regulated. The epigenome is a record of chemical modifications that can turn genes “on” or “off” in response to their environment or disease state. The transcriptome is a collection of all gene readouts within the cell. The study of transcriptome reveals which genes are turned “on” and “off” in a given cell in response to their environment or disease state.
In preliminary studies, Dr. Jaroslav Bendl and colleagues used brain tissue from individuals with Alzheimer’s and cognitively unimpaired individuals. These datasets were leveraged from the Mount Sinai AMP-AD project (Accelerating Medicines Partnership Alzheimer’s Disease, for which the Alzheimer’s Association is a contributing partner), a public and private partnership - launched by the National Institutes of Health in 2014 - that focuses on discovering novel and clinically relevant therapeutic targets. The researchers analyzed these datasets and identified several genetic changes and gene activity patterns from different types of brain cells across different brain regions.
Dr. Bendl and colleagues will leverage their preliminary findings from the brain tissue from the Mount Sinai AMP-AD datasets to identify regions in the DNA (genetic material) that could turn genes “on” or “off” that may be associated with the risk of developing Alzheimer’s. The researchers will also analyze the epigenome and transcriptome in ten different brain cell types from two brain regions impacted in Alzheimer’s from individuals with Alzheimer’s and cognitively unimpaired individuals.
Furthermore, Dr. Bendl’s team will apply sophisticated computer science techniques to identify other brain regions with epigenomic and transcriptomic activities that may be associated with the progression of Alzheimer’s.
The study results may identify regions in the DNA that may be associated with turning genes “on” and “off” in Alzheimer’s. The findings may also help us understand the biological mechanisms by which genes are turned “on” and “off” during the progression of Alzheimer’s.
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