Gene variants may increase susceptibility to accumulate Alzheimer's protein tau

March 03, 2020

ROCHESTER, Minn. -- The toxic protein tau is a key biological feature in the brains of people with Alzheimer's disease. Yet the factors that make people susceptible or resistant to tau accumulation are not well-understood. A preliminary Mayo Clinic study shows that inherited DNA variants may be associated with developing tau deposits in older adults. The research will be presented at the American Academy of Neurology's 72nd Annual Meeting in Toronto April 25-May 1.

"The location and burden of tau in the brain is closely related to cognitive symptoms in Alzheimer's disease, but we don't know nearly enough about how and why tau accumulates the way it does," says first author Vijay Ramanan, M.D., Ph.D., a behavioral neurology fellow at Mayo Clinic. "These findings point to genetic factors being key in that process, which may help us better predict who will develop symptoms and hopefully identify new targets for treatment," Dr. Ramanan says.

The study included 754 people over 50, with an average age of 72, from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota. Of those, 87% had no memory or thinking problems. Researchers studied the participants' genetic profiles and used positron emission tomography (PET) scans to look for tau proteins in their brains.

The study found that participants with novel genetic variants on chromosomes 1 and 5 had a higher amount of tau in their brains, compared with people who had more typical gene sequences in those regions. The genetic variants were found in 2% to 3% of the group, and those participants had about 10% higher tau levels than those without the variants.

The data also confirmed that variants in the microtubule-associated protein tau (MAPT) gene, which produces tau protein, were associated with tau levels and suggested that genes previously linked to risk of Alzheimer's disease dementia, including apolipoprotein E (APOE), are not associated with tau accumulation.

"We are excited that the availability of tau imaging in the Mayo Clinic Study of Aging has allowed us to investigate the genetic architecture underlying tau deposition that may be distinct from the genetic architecture underlying amyloid deposition ? both key proteins underlying Alzheimer's disease dementia," says Prashanthi Vemuri, Ph.D., an Alzheimer's researcher at Mayo Clinic and senior author.
-end-
The study was supported by the National Institutes of Health; the Gerald and Henrietta Rauenhorst Foundation; Alexander Family Alzheimer's Disease Research Professorship of Mayo Clinic; Mayo Foundation for Medical Education and Research; Liston Award; Elsie and Marvin Dekelboum Family Foundation; Schuler Foundation; and Avid Radiopharmaceuticals, which supplied the imaging agent that allows researchers to detect tau in the brain.

Co-authors ? all from Mayo Clinic ? are Xuewei Wang, Ph.D.; Scott Przybelski; Sheelakumari Raghavan, Ph.D.; David Knopman, M.D.; Jonathan Graff-Radford, M.D.; Val Lowe, M.D.; Michelle Mielke, Ph.D.; Clifford Jack Jr., M.D.; Ronald Petersen, M.D., Ph.D.; and Owen Ross, Ph.D.

About Mayo Clinic

Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news and An Inside Look at Mayo Clinic for more information about Mayo.

Media contact:

Susan Barber Lindquist, Mayo Clinic Public Affairs, 507-284-5005, newsbureau@mayo.edu

Mayo Clinic

Related Genetic Variants Articles from Brightsurf:

Researchers identify genetic variants linked to toxic side effects from bevacizumab
In the largest study of its kind, researchers have found two common genetic variants that can be used to predict whether or not cancer patients might suffer severe adverse side-effects, such as high blood pressure, from the drug bevacizumab.

Genetic risk of developing obesity is driven by variants that affect the brain
Some people are at higher risk of developing obesity because they possess genetic variants that affect how the brain processes sensory information and regulates feeding and behavior.

Genetic background influences disease risk from single-gene variants
Life can change dramatically when someone learns they are genetically predisposed to a disease.

Researchers identify novel genetic variants linked to type-2 diabetes
After examining the genes of more than 200,000 people all over the world who have type-2 diabetes, researchers from the Perelman School of Medicine at the University of Pennsylvania and the Veterans Health Administration's Corporal Michael J.

FSU researchers help discover new genetic variants that cause heart disease in infants
Florida State University researchers working in an international collaboration have identified new genetic variants that cause heart disease in infants, and their research has led to novel insights into the role of a protein that affects how the heart pumps blood.

Twenty four genetic variants linked to heightened womb cancer risk
Twenty four common variations in genes coding for cell growth and death, the processing of oestrogen, and gene control factors may be linked to a heightened risk of developing womb (endometrial) cancer, indicates the most comprehensive review of the published evidence so far in the Journal of Medical Genetics.

Genetic variants reduce risk of Alzheimer's disease
A DNA study of over 10,000 people by UCL scientists has identified a class of gene variants that appear to protect against Alzheimer's disease.

Rare genetic variants predispose to sudden cardiac death
By identifying rare DNA variants that substantially increase risk of sudden cardiac death, researchers have laid the foundation for efforts to identify individuals who could benefit from prevention strategies prior to experiencing symptoms.

Genetic variants for autism linked to higher rates of self-harm and childhood maltreatment
People with a higher genetic likelihood of autism are more likely to report higher childhood maltreatment, self-harm and suicidal thoughts according to a new study by researchers at the University of Cambridge.

Genetic variants with possible positive implications for lifestyle
A German and British research team lead by the Technical University of Munich (TUM) has examined the interplay between genetics, cardiovascular disease and educational attainment in a major population study.

Read More: Genetic Variants News and Genetic Variants Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.