“We are looking for the genetic basis so as to better understand all the different types of biology that may be responsible for Alzheimer’s disease.” — Dr. Sudha Seshadri, founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, UT Health San Antonio. Credit: UT Health San Antonio

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Twenty-one million. That’s the number of genetic variations in the human genome that researchers are sifting through to identify patterns predisposing people to Alzheimer’s disease.

Thanks to international collaboration being advanced by faculty of The University of Texas Health Science Center at 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 grew 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.

It’s a huge haystack, and Alzheimer’s-related genetic variations, like needles, are miniscule in comparison. Dr. Sudha Seshadri, Habil Zare, Ph.D., and other faculty at the UT Health San Antonio Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases are investigators on a global project to help answer many of Alzheimer’s riddles.

Seshadri is a founding principal investigator of the International Genomics of Alzheimer’s Project, or IGAP. Biggs Institute faculty contributed data for the newest research from IGAP, published in Nature Genetics, and helped craft worldwide discussion on implications of the findings.

Large sample

Genomic data of half a million people were used in this latest IGAP study, including 30,000 people with confirmed Alzheimer’s disease and 47,000 people categorized as proxies.

“In Alzheimer’s disease research you need many samples, because some of these variants are very rare, and if you want to detect them, you need to study many, many people,” said Zare, assistant professor of cell systems and anatomy in the 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 was established for such kind of collaboration.”

“We are looking for the genetic basis so as 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 in the Long School of Medicine. “As we include data from more and more people, we are able to find variants that are fairly rare, that are only seen in 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 journal publication on April 4, 2022, 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 described before.

Diversity needed

The study published in Nature Genetics is confined to certain people groups, which makes it impossible to generalize the gene variations worldwide.

“One of the challenges with this paper, as well, is it is largely in persons of European ancestry,” Seshadri said. “So we hope to bring, over the next few years, a much larger sample of Hispanic and other minority populations to further improve gene discovery.”

The South Texas Alzheimer’s Disease Research Center (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 bring the region’s sizable Hispanic population into genetic studies and other initiatives such as clinical trials. ADRCs are National Institute on Aging Centers of Excellence.

Older Hispanic adults are estimated to be at 1.5 times greater risk of Alzheimer’s and other dementias than non-Hispanic whites. Dementia is costing 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, the researchers acknowledge the partners who play significant roles.

“We would like to thank each of the collaborators within IGAP, and all the patients and families that join such studies, and the National Institute on Aging, which is our funder,” Seshadri said.

Read about this research finding that increases the world’s knowledge of Alzheimer’s disease and sparks drug potential.

The Glenn Biggs Institute for Alzheimer’s 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 treatment through clinical trials and research.

UT Health San Antonio, South Texas’ largest research university, has an annual research portfolio of $350 million and a Department of Education designation as a Hispanic-Serving Institution. Its Long School of Medicine is listed among U.S. News & World Report’s best medical schools, ranking in the top 30% nationwide for research.

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UT Health San Antonio

UT Health San Antonio, with a more than $360 million annual research portfolio, is South Texas’ largest academic research institution, a primary driver for San Antonio’s health care and biosciences...