UT Health San Antonio finds genetic risk factor overlap between Alzheimer’s disease, and all cause and vascular dementias

Researchers achieve largest-ever genome-wide association study of its kind

Contact: Steven Lee, (210) 450-3823, [email protected]

SAN ANTONIO, Sept. 17, 2024 - In landmark research, scientists at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) have reported the largest-ever genome-wide association study of dementia from all causes, revealing an overlap of genetic risks including neurodegeneration, vascular factors and cerebral small-vessel disease.

Genome-wide association studies help scientists identify genes associated with a particular disease or trait by exploring the entire set of DNA, or genome, of a large group of people - in this case, a dataset of 800,597 individuals, with 46,902 and 8,702 cases of all-cause dementia and vascular dementia, respectively.

"Dementia is a multifactorial disease with Alzheimer's disease and vascular dementia pathologies making the largest contributions - and yet, most genome-wide association studies focus just on Alzheimer's disease," said Bernard Fongang, PhD, with the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases at UT Health San Antonio. "We conducted such a study of all-cause dementia and discovered a substantial genetic overlap with vascular dementia."

Fongang, who also is with the departments of biochemistry and structural biology, and population health sciences, at the Joe R. and Teresa Lozano Long School of Medicine at UT Health San Antonio, is corresponding contact for the study titled, "A genome-wide association meta-analysis of all-cause and vascular dementia," published July 24 by Alzheimer's & Dementia: The Journal of the Alzheimer's Association. The study author is credited as the Mega Vascular Cognitive Impairment and Dementia (MEGAVCID) consortium, which is an international consortium of cohorts focusing on the genetics of vascular cognitive impairment and dementia.

Two clinically distinct dementias

According to the study, Alzheimer's disease traditionally is considered the most common dementia subtype, followed by vascular dementia. The two conditions are clinically distinct, however.

Vascular dementia is diagnosed based on the presence of stroke or extensive cerebral vascular disease, with atherosclerosis and arteriolosclerosis considered the underlying pathologies. But a wealth of evidence from recent years has emphasized a broad role for brain vascular damage as a major mechanism for cognitive impairment.

It now is increasingly recognized that a component of vascular pathology is prominent in all major dementias and acts synergistically with amyloid beta, tau and other neurodegenerative pathologies to affect dementia risk, the study notes.

Because most genome-wide association studies have focused on Alzheimer's disease, highlighting multiple genetic risk variants, Fongang's team conducted such a study of all-cause dementia and examined the genetic overlap with vascular dementia.

Its vast dataset drew from individuals comprising the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), the Alzheimer's Disease Genetics Consortium (ADGC), the European Alzheimer Disease Biobank (EADB) and the UK Biobank (UKBB), encompassing four different reported ancestries: European (98.5%), African (1.0%), Asian (0.4%) and Hispanics/Latino (0.1%).

Known genetic variants associated with Alzheimer's disease were replicated for all-cause dementia and vascular dementia. Functional analysis revealed the overlap of genetic risks of all-cause dementia with neurodegeneration, vascular risk factors such as hypertension and diabetes, and cerebral small vessel disease.

Essentially, known genetic variants for Alzheimer's disease were identified as risk factors for all-cause dementia and vascular dementia.

"Our findings expand the current knowledge base of dementia genetics by focusing on both all-cause dementia and vascular dementia," Fongang said. "We identified several putative genetic variants and biological pathways associated with all-cause dementia and vascular dementia, and added additional support for the involvement of vascular mechanisms in dementia pathogenesis."

The study concluded that the results should be validated in additional datasets including non-European individuals. UT Health San Antonio is the largest academic research institution in South Texas, with an annual research portfolio of $413 million.

A genome-wide association meta-analysis of all-cause and vascular dementia

Mega Vascular Cognitive Impairment and Dementia (MEGAVCID) consortium

First published: July 24, 2024, Alzheimer's & Dementia: The Journal of the Alzheimer's Association

Link to full study: https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.14115

The University of Texas Health Science Center at San Antonio (UT Health San Antonio), a primary driver of San Antonio's $44.1 billion health care and biosciences sector, is the largest academic research institution in South Texas with an annual research portfolio of $413 million. Driving substantial economic impact with its six professional schools, a diverse workforce of more than 8,500, an annual expense budget of $1.46 billion and clinical practices that provide 2.6 million patient visits each year, UT Health San Antonio plans to add more than 1,500 higher-wage jobs over the next five years to serve San Antonio, Bexar County and South Texas. To learn about the many ways "We make lives better®," visit UTHealthSA.org.

The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases is dedicated to providing comprehensive dementia care while advancing treatment through clinical trials and research. The Biggs Institute is a National Institute on Aging (NIA)-designated Alzheimer's Disease Research Center (ADRC). In addition to patient care and research, the Biggs Institute partners with the School of Nursing at UT Health Science Center San Antonio to offer the Caring for the Caregiver program.

The UT Health San Antonio Joe R. and Teresa Lozano Long School of Medicine is listed among U.S. News & World Report's best medical schools, ranking in the top 30% nationwide for research. To learn more, visit https://uthscsa.edu/medicine/.

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