Key Points
- Scientists at the National Institutes of Health (NIH) have discovered new genetic risk factors for two types of dementia.
- The team used cutting-edge technology to identify large-scale DNA changes, known as structural variants, in thousands of DNA samples.
- The researchers found several structural variants that could be linked to Lewy body dementia (LBD) and frontotemporal dementia (FTD).
Scientists at the National Institutes of Health (NIH) have made a breakthrough in the study of dementia. They have identified genetic risk factors for two types of dementia, Lewy body dementia (LBD) and frontotemporal dementia (FTD), by analyzing thousands of DNA samples.
The scientists used a unique approach to identify large-scale changes in the DNA code, called structural variants, which are more challenging to study than smaller genetic mutations. Structural variants can consist of at least 50, but often hundreds or even thousands of nucleotides at once. The team used cutting-edge computer algorithms to map these structural variations across the whole genome, combined with machine learning.
The team’s analysis identified several structural variants that could be linked to the development of LBD and FTD. Notably, they discovered a new variant in the TCPN1 gene, associated with a higher risk of developing LBD. The variant is already known to be a risk factor for Alzheimer’s disease, which suggests that this structural variant may also play a role in other types of dementia.
The team also examined 50 genes linked to inherited neurodegenerative diseases and identified additional rare structural variants, including several that are known to cause disease. Their work confirmed two well-established risk factors for FTD changes in the C9orf72 and MAPT genes, which further supported the study’s findings.
To make these findings more accessible to the scientific community, the researchers generated a catalog based on their analysis data, and they created an interactive app to enable scientists to study their genes of interest and identify which variants are present in controls versus LBD or FTD cases.
Dr. Sonja W. Scholz, one of the scientists on the project, described the findings as “a very exciting finding” from a genetics standpoint. She said that it “provides a point of reference for cell biology and animal model studies and possibly down the road, a target for intervention.”
The team’s research may have significant implications for the scientific community’s understanding of the mechanisms behind neuronal cell death or dysfunction, paving the way for more precise treatments for debilitating and fatal disorders like LBD and FTD.
Dr. Bryan J. Traynor, a senior investigator at NIA, said that “with each discovery, we shed light on the mechanisms behind neuronal cell death or dysfunction, paving the way for precision medicine to combat these debilitating and fatal disorders.”
The research was supported in part by the Intramural Research Program at NINDS and NIA. The scientists expect the dataset to continue growing as they analyze more data.
