National Institutes of Health scientists recently identified genetic risk factors for two types of non-Alzheimer's dementia.
The scientists identified several structural variants as genetic risk factors for Lewy body dementia and frontotemporal dementia through analysis of thousands of DNA samples, according to a May 8 news release.
"If you imagine that our entire genetic code is a book, a structural variant would be a paragraph, page or even an entire chapter that has been removed, duplicated or inserted in the wrong place," Dr. Sonja W. Scholz, M.D., Ph.D., investigator in the neurogenetics branch of NINDS and senior author of the study, said in the release.
The study's findings, published in Cell Genomics, detail how researchers identified large-scale DNA changes, known as structural variants, in the DNA samples that could be risk factors for the two types of dementia, the release reported. The study was a collaboration between National Institute of Neurological Disorders and Stroke scientists and the National Institute on Aging at NIH.
The study isn't the first time structural variants have been implicated in a variety of neurological disorders, according to the release. However, unlike more commonly studied mutations that often affect one or a few DNA building blocks or nucleotides, structural variants represent up to thousands of nucleotides at once, which makes them more challenging to study.
The research team investigated whole-genome data from the patient DNA samples and several thousand unaffected controls through state-of-the-art computer techniques that can map structural alterations across an entire genome via machine learning, the release said.
Through samples from patients suffering Lewy body dementia which, like Parkinson's disease, is linked to aberrant deposits of the protein alpha-synuclein in the brain, scientists discovered a previously unidentified mutation in the TCPN1 gene, the release reported. The variation in which the gene has more than 300 nucleotides deleted has been linked to a greater risk of Lewy body dementia.
TCPN1 is a known risk factor for Alzheimer's disease, the release said. Even if this finding is novel for Lewy body dementia, it's possible this structural variant also affects people with other forms of dementia.
“Research to unravel the intricate genetic architecture of neurodegenerative diseases is resulting in significant advances in scientific understanding,” Bryan J. Traynor, M.D., Ph.D., senior investigator at NIA, said in the release. “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."
