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Twenty one million. It’s the number of genetic variations in the human genome that researchers sift through to identify patterns that predispose people to Alzheimer’s disease.
Thanks to an international collaboration advanced by faculty at Texas Health Science Center San Antonio, also known as UT Health San Antonio, more genetic variations for Alzheimer’s disease are known today than ever before. The list of gene variants recognized for late-onset Alzheimer’s disease has grown from one in 2009 to 40 in 2022, and this spring scientists published an expanded list of 75, some of which are considered prime drug targets.
That’s a huge haystack, and the genetic variations associated with Alzheimer’s, like the needles, pale in comparison. Dr. Sudha Seshadri, Habil Zare, Ph.D., and other faculty at the UT Health San Antonio Glenn Biggs Institute for Alzheimer and Neurodegenerative Diseases are researchers on a global project that is helping to answer many of Alzheimer’s mysteries.
Seshadri is the founder and principal investigator of the International Alzheimer’s Genomics Project, or IGAP. Biggs Institute faculty contributed data to the latest research from IGAP, published in Nature Genetics, and helped organize a global discussion about the implications of the findings.
A large sample
This latest IGAP study used genomic data from half a million people, including 30,000 people with confirmed Alzheimer’s disease and 47,000 people categorized as proxies.
“In studying Alzheimer’s disease, you need a lot of samples because some of these variants are very rare, and if you want to find them, you have to study many, many people,” said Zare, assistant professor of cellular systems and anatomy at Joe. R. and Teresa Lozano Long School of Medicine and an expert in computational biology and bioinformatics. “The only way to get there is through collaboration between centers and consortia, and IGAP is designed for that kind of collaboration.”
“We’re looking for the genetic basis to better understand all the different types of biology that may be responsible for Alzheimer’s disease,” said Seshadri, founding director of the Biggs Institute and professor of neurology at the Long School of Medicine. “As we include data from more and more people, we can find variants that are quite rare, occurring in only about 1% of the population.”
In 2009, the year of the first genome-wide association studies, researchers knew of one gene called APOE associated with late-onset Alzheimer’s disease. Before the journal’s April 4, 2022 publication, the researchers had a list of 40 such genes. This new paper confirmed 33 of them in a larger population sample and added 42 new genetic variants not previously described.
Variety is needed
The study, published in Nature Genetics, was limited to specific groups of people, making it impossible to generalize about gene variation worldwide.
“One of the challenges with this paper is also that it is largely about people of European descent,” Seshadri said. “So we’re hoping to bring in, over the next few years, a much larger sample of Hispanic and other minority populations to further improve gene discovery.”
The Alzheimer’s Disease Research Center of South Texas (ADRC), a collaboration of the Glenn Biggs Institute at UT Health San Antonio and the University of Texas Rio Grande Valley, is on a mission to engage the region’s significant Hispanic population in genetic research and other initiatives such as clinical trials. ADRCs are Centers of Excellence of the National Institute on Aging.
Hispanic adults are estimated to be 1.5 times more likely to develop Alzheimer’s and other dementias than non-Hispanic whites. Dementia costs individuals, caregivers, families and the nation an estimated $321 billion in 2022, according to the Alzheimer’s Association.
As the quest to end the suffering endured by individuals and families continues, researchers are recognizing partners who play a significant role.
“We would like to thank each of the collaborators within IGAP and all the patients and families who join such studies, as well as the National Institute on Aging, which is our funder,” said Seshadri.
Read about this research that increases the world’s knowledge of Alzheimer’s disease and ignites the potential for cures.
The Glenn Biggs Institute for Alzheimer’s Disease and Neurodegenerative Diseases at UT Health San Antonio is a National Institute on Aging-designated Alzheimer’s Disease Research Center dedicated to providing comprehensive dementia care while advancing treatments through clinical trials and research .
UT Health San Antonio, the largest research university in South Texas, has an annual research portfolio of $350 million and is designated by the Department of Education as a Latino-serving institution. Its Long School of Medicine is listed among US News & World Report’s top medical schools, ranking in the top 30% nationwide for research.
Learn more about how UT Health San Antonio is doing what it takes to make lives better.