Unraveling Alzheimer’s: Discovery of 17 New Genetic Variants

Unraveling Alzheimer’s: Discovery of 17 New Genetic Variants
The groundbreaking discovery of 17 new genetic variants associated with Alzheimer’s disease has opened up new possibilities for understanding the genetic underpinnings of this devastating condition. Genetic variants play a crucial role in the development and progression of Alzheimer’s, and the identification of these 17 new variants represents a significant leap forward in our understanding of the disease. By unraveling the genetic complexity of Alzheimer’s, researchers are gaining valuable insights into potential targets for future treatments and interventions. This discovery has the potential to revolutionize our approach to Alzheimer’s research and pave the way for more personalized and effective therapies tailored to an individual’s genetic profile.
Unraveling Alzheimer’s: Discovery of 17 New Genetic Variants
The recent breakthrough in Alzheimer’s research has led to the identification of 17 previously unknown genetic variations linked to the disease, shedding new light on the complex genetic landscape of Alzheimer’s. These genetic variations, or alleles, have the potential to significantly impact an individual’s risk of developing Alzheimer’s, providing valuable clues for understanding the underlying genetic mechanisms at play. The discovery of these 17 new genetic variants represents a major step forward in our quest to unravel the genetic mysteries of Alzheimer’s and develop targeted treatments based on an individual’s unique genetic makeup. This groundbreaking research has the potential to revolutionize our understanding of Alzheimer’s and pave the way for more personalized and effective interventions tailored to an individual’s genetic profile.

Genetic Variants and Alzheimer’s Disease

Previous studies have shown that genetics may play a significant role in the development of Alzheimer’s disease. Recently, researchers have identified 17 genetic variants associated with Alzheimer’s disease in five genomic regions. These findings included genetic variant data from ethnic groups that have been historically underrepresented in genetic studies regarding Alzheimer’s. Over the past few years, more research has supported the idea that genetics may play a role in the development of Alzheimer’s disease (AD) — a type of dementia affecting about 32 million people globally. The study was recently published in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. While scientists are still not completely sure what causes Alzheimer’s disease, most believe it develops from a combination of factors including genetics, age-related changes in the brain, and certain lifestyle and environmental factors. For example, a study published in April 2022 identified 75 gene locations correlated to an increased risk for Alzheimer’s disease, among them 42 locations that had not been previously linked to the condition. Research published in February 2023 discovered a genetic variant often found in people of African ancestry may heighten Alzheimer’s disease risk. A study published in September 2023 reported a genetic mutation within the brain’s immune cells that might increase a person’s risk for Alzheimer’s disease.

17 New Genetic Variants Identified

For this study, researchers used whole genome sequencing data from the Alzheimer’s Disease Sequencing Project (ADSP) — a genetics initiative launched by the National Institutes of Health in 2012 as part of the National Alzheimer’s Project Act. Scientists had access to information on more than 95 million genetic variants from almost 4,600 people with or without Alzheimer’s disease. After analyzing the data, study researchers uncovered 17 significant variants associated with Alzheimer’s disease located in five genomic regions. Whole genome sequence data provides information on every change (variation) in the DNA sequence of the study participants and enables researchers to refine the information from GWAS studies as well as make novel discoveries. One analogy is to compare the DNA sequence in the human genome to the string of letters that make up a book. Earlier GWAS studies identified common ‘spelling errors’ and brought researchers to the specific pages where important errors occurred but did not identify every letter that changed or was missing. With whole genome sequencing, researchers are looking at every letter on the page and more comprehensively understanding all the changes and ‘spelling errors.’

KAT8 Genetic Variant and Alzheimer’s Risk

One of the most notable genetic variants identified was the lysine acetyltransferase 8 (KAT8) variant. Past studies show that KAT8 is important for cerebral development and may play a role in the development of Alzheimer’s disease-related dementias and Parkinson’s disease. Additionally, through the ADSP database, the research team had access to genetic variant data from a wide range of ethnicities, including Black/African-American Hispanic/Latino, which researchers say have been historically underrepresented in genetic studies regarding Alzheimer’s disease. Historically, the vast majority of individuals included in genetic studies of Alzheimer’s disease have been of European ancestry. We know that the prevalence of Alzheimer’s disease varies across population groups, with African-Americans having a higher prevalence. So to understand the full spectrum of Alzheimer’s disease risk, it is important for studies to represent diverse genetic ancestry and diverse environments in terms of social determinants of health.

RESULT

Genetic variants play a significant role in the development and progression of Alzheimer’s disease. Understanding the impact of specific gene variants, such as APP A673T, PSEN1 E280A, and CLU rs11136000, can provide valuable insights into the risk and protective factors associated with Alzheimer’s. Further research into these genetic variants is crucial for the development of targeted therapies and personalized treatment approaches for individuals at risk of developing Alzheimer’s disease.