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Sonja W. Scholz, MD, PhD, Is Uncovering the Molecular, Genetic Basis of Lewy Body Dementia

Article In Brief

The recipient of the AAN Norman Geschwind Prize for Behavioral Neurology discussed the trajectory of her research into the molecular and genetic basis of Lewy body dementia, which brought her from medical school in Austria to work in a neurogenetics laboratory at the National Institute of Neurological Disorders and Stroke.

“I'm an optimist,” said Sonja W. Scholz, MD, PhD. “I'm hopeful that during my professional life we will get to disease modification, not just for Lewy body dementia but for all these complex neurodegenerative diseases.”

Optimism—along with what one of her mentors calls her “inability to take no for an answer”—go far in explaining why Dr. Scholz, a tenure-track investigator in the neurogenetics branch at the National Institute for Neurological Disorders and Stroke, was awarded the Norman Geschwind Prize in Behavioral Neurology at AAN's Annual Meeting in Philadelphia.

Her laboratory is searching for genes underlying complex neurodegenerative disorders, in particular Lewy body dementia (LBD). The fact that it is under-studied and under-recognized by clinicians and the public alike is actually what attracted her to study LBD.

“It's a bit of a personality thing,” she told Neurology Today. “There's a tendency to shy away and say there's nothing that can be done. I tend to be the opposite. I don't want to take the quick route for reward. I want to study complex patients and make a difference. That would be the most rewarding thing I could see myself doing with my life.”

Her Journey Forward

Dr. Scholz obtained her medical degree from the Medical University of Innsbruck in Austria, where she saw her first patients with LBD.

“I didn't even have a full understanding of what Lewy body dementia was,” she recalled, “but once I started to hear the stories of all their problems, their panic attacks, their syncope attacks, the psychiatric problems that these patients and their families have to live with, that's when I realized what an awful disease this is. It made a huge impression on me.”

Leaving Austria for the United States, Dr. Scholz pursued a post-doctoral fellowship at the Laboratory of Neurogenetics of the National Institute of Aging (NIA) under the supervision of Andrew B. Singleton, PhD, and John Hardy, PhD. [Dr. Hardy is now chair in the department of neuroscience at University College London.]

“Sonja is absolutely and completely committed to making a difference in the diseases she works on,” said Dr. Singleton. “I've worked with her for a decade or more now, and it's been absolutely wonderful to see her progress. I think her success has been driven in part by an inability to take no for an answer. She is smart and relentless and great fun to work with. I am so pleased that the AAN recognized her with this award.”

Dr. Scholz went from the NIA to the University College of London, UK, where she obtained a PhD in neurogenomics in 2010. Her next stop was to Johns Hopkins University School of Medicine, where she completed her neurology residency training.

“Sonja came to Johns Hopkins as a resident who was already a very productive scientist,” said Argye E. Hillis, MD, professor of neurology and executive vice chair of neurology, at Johns Hopkins. “During her residency she developed into an outstanding clinical neurologist as well. Through support from an NINDS-funded R25 research education grant and mentoring from clinician-scientists, she developed into a superb clinician-scientist. Her subsequent research has flourished at NIH. Unlike many highly productive investigators, she has sought out opportunities to continue clinical care of people with dementia and movement disorders, both at NIH and Johns Hopkins.”

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“There's a tendency to shy away and say there's nothing that can be done. I tend to be the opposite. I don't want to take the quick route for reward. I want to study complex patients and make a difference. That would be the most rewarding thing I could see myself doing with my life.”

—DR. SONJA W. SCHOLZ

The Research

In 2016, Dr. Scholz was the senior author of a paper in Neurobiology of Disease that used next-generation sequencing to reveal a substantial genetic contribution to LBD. In a cohort of 111 pathologically confirmed LBD patients, compared with 222 controls, she reported that about 25 percent of cases carried a pathogenic mutation or risk variant in amyloid precursor protein (APP), glucocerebrosidase (GBA), or presenilin 1 (PSEN1). In particular, 13 percent carried a pathogenic mutation in GBA, 10 percent had a risk variation or mutation in PSEN1, and 2 percent had an APP mutation. The apolipoprotein E4 risk allele was also significantly overrepresented in LBD patients (p <0.001)

Dr. Scholz's laboratory has also shown that much of the genetic risk for LBD overlaps with that for both Parkinson's disease and Alzheimer's disease. Mutations in GBA have been detected in both PD and LBD. Clinical trials are in the pipeline, she said, to treat the defect by boosting the GBA gene.

“I'm leading a large multicenter international effort where we perform genome sequencing of a large cohort of 3,000 cases and healthy controls for a whole range of analyses, including machine learning,” she said. “It's challenging working in a field that is relatively under-served. I'm very grateful that AAN recognizes these efforts.”

“LBD is an extremely heterogeneous disease, much more so than Alzheimer's disease,” she said. “It's very difficult to diagnose the patients in the early stage. They can develop anything from mood disorders to thought disorders, so they might go to a psychiatrist. Other patients develop motor problems that looks like Parkinson's disease. Still others start out having sleep problems and might see a sleep specialist. They might even start out seeing a cardiologist due to autonomic dysfunction.”

Dr. Scholz is married to Bryan Traynor, MD, PhD, another neurologist who also studies neurodegeneration at NIH. “We are two nerds,” she said with a laugh.

With a better understanding of the genetic and molecular basis of LBD and other neurodegenerative disorders, Dr. Scholz said, earlier diagnosis and treatment should one day be possible. About that, she is most optimistic.

Link Up for More Information

• Geiger JT, Ding J, Crain B, et al. Next-generation sequencing reveals substantial genetic contribution to dementia with Lewy bodies https://www.sciencedirect.com/science/article/pii/S0969996116301371?via%3Dihub. Neurobiol Dis 2016; 94:55–62.