Could dysfunction of structures inside cells that make energy contribute to the progression of Alzheimer’s?
Shea Andrews, Ph.D.
Icahn School of Medicine at Mount Sinai
New York, NY - United States
Recent studies suggest that specialized structures inside cells called mitochondria – a powerhouse of energy generation for cells – may undergo damage early on, in Alzheimer's. However, it is unknown whether mitochondria dysfunction leads to impairments in Alzheimer’s, or if it is a by-product of Alzheimer’s. Mitochondria contain their own genetic material (DNA) that is distinct from that of rest of the cell. Researchers can measure levels of mitochondrial DNA to study the health of a cell and its mitochondria. This measurement is called mitochondrial DNA copy number, or “mtDNA-CN.”
Variations in certain genes may be associated with a person’s risk of developing Alzheimer’s. Using statistical techniques, researchers can calculate a “polygenic risk score” (or “PRS”) which is a measure that analyzes small changes in genes in the DNA to assess a person’s risk of developing a disease. Another measure, called Mendelian randomization (MR), can help researchers understand how gene variations may cause disease outcomes. Dr. Shea Andrews will use these measurements to evaluate the impact of mitochondria dysfunction on the risk of developing Alzheimer’s.
To conduct their study, the researchers will analyze genetic data from 20,000 participants in the Alzheimer’s Disease Sequencing Project (an ongoing Alzheimer’s and other genetics study) and 60,000 participants from two additional large biorepositories that stores biological samples for use in research (the Mount Sinai BioMe biobank and the UK Biobank), which include people with and without Alzheimer’s.
First, Dr. Andrews and colleagues will measure levels of mitochondrial DNA in participants and determine whether there is an association between those levels and the development of Alzheimer’s. Next, the researchers will use one of the measures (PRS) to investigate whether mitochondrial DNA levels are associated with an increased risk of developing Alzheimer’s.
Dr. Andrews and colleagues will subsequently use the MR to determine whether mitochondrial DNA levels contribute to a person’s risk of developing Alzheimer’s, or whether Alzheimer’s may be impacting changes in those levels.
If successful, this study results may provide insights into the association between the dysfunction of energy production and Alzheimer’s. It could also help researchers determine whether targeting mitochondrial DNA levels might be a potentially therapeutic strategy in Alzheimer’s.
This project was made possible by the Dale Schenk Alzheimer's Association Research Roundtable Award.
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