Novel Therapeutics and Advanced Diagnostics > Pioneering a Precision Approach to Neurological Diseases

Pioneering a Precision Approach to Neurological Diseases

By Christina Hernandez Sherwood Photography by Paul Flessland

There’s no master key that will unlock the cure for Alzheimer’s disease. Instead, researchers are forging, one by one, single keys that are opening new pathways to treatments and, perhaps, cures for Alzheimer’s and related neurodegenerative diseases.

Doctors will one day diagnose and treat diseases like Alzheimer’s the same way as many cancers — by precision approaches, says physician-scientist Nilüfer Ertekin-Taner, M.D., Ph.D., a neuroscientist, behavioral neurologist and chair of the Department of Neuroscience at Mayo Clinic. “The end game is classifying patients by their disease type and putting them on the right medicine,” she says. “This is precision medicine, and this is what we’re after.”

Dr. Ertekin-Taner’s mission is to uncover diagnostics and treatments for neurodegenerative diseases that affect millions and that currently take too long to diagnose, have too few treatments and have no cures. Her work conducting groundbreaking research into the genomic underpinnings of Alzheimer’s and related conditions has already led to more accurate diagnostic approaches and more therapeutic targets.

“We have seen the field come a long way,” says Dr. Ertekin-Taner, who has watched basic science discoveries from her lab, and others around the world, advance enough to translate to patient care. “That gives me tremendous hope that the best is yet to come.”

Tracing Genetic Pathways

Researchers first began to chip away at the genetics of neurodegenerative diseases, Dr. Ertekin-Taner says, when they discovered that certain conditions, including Alzheimer’s, amyotrophic lateral sclerosis (ALS), Lewy body dementia and Parkinson’s disease, sometimes occur in families.

But that only got them so far. The vast majority of neurodegenerative disease cases have some other contributing cause. In fact, there are hundreds of genetic factors related to these diseases. “Each patient with neurodegenerative disease gets their disease for their own set of reasons,” Dr. Ertekin-Taner says.

We have seen the field come a long way. That gives me tremendous hope that the best is yet to come.
— Nilüfer Ertekin-Taner, M.D., Ph.D.

Think of a balance scale. On one side are the genomic and environmental factors, such as exposure to air pollution, that increase one’s risk of developing a neurodegenerative disease. On the other side are protective factors. Depending on which way the scale tips, a person is either predisposed to or protected from the common, complex forms of these diseases. The only way to identify these hundreds of risk factors is by studying broad patient populations.

In her large multisite, multi-institutional projects, Dr. Ertekin-Taner leverages hundreds of thousands of brain samples from the Mayo Clinic Brain Bank and blood specimens from Mayo Clinic patients to generate deep genomic data. Thanks to the power of data repositories and infrastructure like those within Mayo Clinic Platform, she can also access clinical information, such as cognitive data and other diagnoses, to consider alongside a genetic profile. This enabled her to be among the first researchers to apply what’s called an endophenotype approach to genomic studies of Alzheimer’s disease. This approach uses measurable biological traits to trace the molecular pathways that link complex genetic features to Alzheimer’s disease.

For instance, Dr. Ertekin-Taner pioneered the use of a small protein fragment known as an amyloid beta peptide as a biomarker for Alzheimer’s. This paved the way for her and other researchers to gain a deeper understanding of the complex biology connected with different facets of this disease — essential to help diagnose and treat Alzheimer’s.

“The Mayo Clinic Department of Neuroscience leads the nation’s largest studies in understanding the molecular underpinnings of these diseases, which is fundamental for us to find cures and diagnostics,” she says.

Still, Dr. Ertekin-Taner acknowledges that currently there are “an unmanageable number of molecular targets to go after” in the effort to develop therapies for neurodegenerative diseases. That’s why, when she became enterprise chair of the department in 2023, Dr. Ertekin-Taner began the process to modernize Mayo Clinic’s 30-year-old brain bank, which contains specimens from more than 11,000 brain donors. The effort includes digitization that will help researchers connect more dots with the assistance of large-scale, artificial intelligence-enabled analytic models.

“The incredible data from the brain bank will become an incessant factory of finding therapeutic targets against which researchers and clinicians can develop therapies,” she says. “We are at a phenomenal time in research.”

A Patient-Centered Mission

Dr. Ertekin-Taner is the daughter of two neurologists who are clinical neurophysiologists. Her father is also a physician-scientist.

“We joke that everything below the neck is them,” she says, “and everything above the neck is me.”

Deciding medicine was a safer career choice than her first love of acting, she attended medical school in her home country of Turkey before seeking further training in neuroscience. “For a curious person,” Dr. Ertekin-Taner says, “the brain is the best organ to study.”

She came to the United States to continue her studies with her husband, C. Burcin Taner, M.D., now chair of the Department of Transplantation at Mayo Clinic in Jacksonville, Florida, because the country had the best opportunities in brain and transplant medicine. After about a decade at Mayo Clinic in Rochester, Minnesota, where Dr. Ertekin-Taner earned her Ph.D. in molecular neuroscience and completed two residencies and two fellowships, the couple were recruited to join Mayo Clinic in Florida, as staff members. “Mayo’s overall mission aligns with mine: discovery and innovation for the sake of patients,” she says.

Despite the demands of her research, Dr. Ertekin-Taner has continued to serve as a behavioral neurologist in the Memory Disorders Clinic at Mayo Clinic in Florida. There, she evaluates and manages patients with Alzheimer’s and other neurodegenerative diseases.

“There was never a question in my mind that I’d continue seeing patients,” she says. “Because that’s what inspires me.”