Across the country, Alzheimer’s disease spreads with disheartening frequency. People living with the condition vanish slowly, first from themselves, then from family members and friends.

Widely recognized as the most common form of dementia, Alzheimer’s is notoriously challenging to diagnose. At one time, only a brain autopsy could confirm its ravages of mind and body. Treatment remains elusive as well. To date, a battery of drugs has demonstrated only partial effectiveness in slowing the disease’s symptoms.

Unbowed by the challenge, researchers at UT Southwestern Medical Center continue to make progress. It’s a race against time. According to the Alzheimer’s Association, more than 6 million Americans currently live with the progressive, memory-robbing disease. By 2050, that number is projected to rise to nearly 13 million.

Responding to one of the greatest health challenges of our time, researchers and clinicians at UT South-western are giving people living with Alzheimer’s disease more than a glimmer of promise.

Finding a Key

When Marc Diamond, M.D., founded the Center for Alzheimer’s and Neurodegenerative Diseases at UT Southwestern, his goal was to find a way to diagnose and treat the disease more effectively. Over the last two decades, the Professor of Neurology and Neuroscience has concentrated on understanding how neurodegenerative conditions such as Alzheimer’s, Parkinson’s, and Lou Gehrig’s disease function at a fundamental level.

The diseases are linked to the accumulation of proteins in the brain that assemble themselves much like Lego bricks. In Alzheimer’s patients, accumulations of excess tau protein are the culprit. Dr. Diamond’s lab determined that clusters of tau proteins self-replicate and spread disease between brain cells. Researchers discovered Alzheimer’s and Parkinson’s exhibit similar characteristics, a revelation that has all but transformed the study of neurodegenerative disease.

Philanthropy has been essential to Dr. Diamond’s vaccine research. This has allowed his group to develop new ways to modify proteins to create antibodies that can be used in treatment. These vaccines are being tested in animal models, and if they are successful, they will move into human trials.

“You can’t do the kind of high-risk, high-reward work we do here without generous private philanthropy,” he said. “Local philanthropy’s support of the big ideas and bold research we are currently doing is truly unbelievable.”

Breaking barriers

As Director of UT Southwestern’s Neuro-Focused Ultrasound Lab, Bhavya R. Shah, M.D., has been spearheading new ways to use MRI-focused ultrasound in the quest to arrest Alzheimer’s. The Assistant Professor of Radiology and Neurological Surgery is bringing myriad skills together with a single goal in mind: opening the blood-brain barrier to enable new ways to diagnose and treat Alzheimer’s disease.

Part of the body’s defenses against toxins and diseases, the blood-brain barrier separates the brain from the bloodstream. Essential nutrients delivered by the blood can pass through the barrier, but larger particles, such as bacteria, viruses, and even drugs, cannot. Using invisible ultrasound waves, Dr. Shah and his team have explored a twofold approach to deliver medications without surgery. Focused ultrasound enables clinicians to temporarily enlarge openings in the blood-brain barrier, allowing physicians to effectively deliver drug therapies. The team is also involved in a clinical trial that uses amyloid molecular imaging technology to detect where abnormal proteins are located in the brain and target those regions.

“Thanks to Dr. Diamond’s comprehensive research, once you fully understand the disease’s complexities, one can develop ways to treat it, especially by using focused ultrasound to deliver therapies,” said Dr. Shah, who hopes within the next year to do a focused opening in the blood-brain barrier with an Alzheimer’s patient.

If that is successful, he hopes the next steps will be to deliver personalized doses of medicine to treat Alzheimer’s and other brain diseases, using a battery of techniques, including immunotherapy and viral gene therapy. He envisions researchers one day building a library of antibodies tuned to fight pathological human proteins, giving physicians a stockpile of tools in the fight against neurodegenerative diseases.

Community support has been essential to Dr. Shah’s work, enabling him to purchase essential equipment and conduct safety and feasibility studies on focused ultrasound techniques.

The Promise of AI

Finding a cure for Alzheimer’s disease may take time, but Ihab Hajjar, M.D., and his team are deploying everything in their arsenal to better understand and attack the disease before it’s too late for individual patients.

Early detection is key, researchers say. While treatments are limited, detecting Alzheimer’s disease before people show signs of memory problems and making the right medical and lifestyle changes can make a difference in how long a patient can stave off full-blown dementia.

“The problem is in the earliest stages of the disease, patients with Alzheimer’s are often able to have regular conversations and communicate with loved ones, and the symptoms of the disease are not easy to identify. In some occasions, they may even perform in the normal or average range on cognitive tests that we use to gauge performance,” said Dr. Hajjar, Professor of Internal Medicine, Neurology, and in the Peter O’Donnell Jr. Brain Institute at UT Southwestern.

That’s why Dr. Hajjar’s latest work, which has been supported by the Pogue Family Foundation, is so promising. Using artificial intelligence, he and his team have detected subtle changes in a patient’s voice that might indicate the disease’s earliest stages. By building a catalog of traits shared by people experiencing mild cognitive impairment, a common Alzheimer’s precursor, the project is evolving into developing a new diagnostic tool that may help physicians detect subtle mental changes that may identify early Alzheimer’s.

"Artificial intelligence can pick up on differences in voice and patterns that the average human can’t pick up on, such as slight and sometimes imperceptible pitch changes and variations in speed that might help determine whether something unhealthy is going on,” Dr. Hajjar said.

Adapting existing technology to detect proteins in the blood that are associated with a greater risk of developing Alzheimer’s is also showing promise, giving physicians and patients more tools to detect the disease and hopefully develop ways to prevent patients from progressing into the disease’s more severe stages.

More tools are needed, but according to Dr. Hajjar, solving the riddle of Alzheimer’s disease ultimately comes down to resources. The Pogue family’s generosity, which helped recruit Dr. Hajjar from Emory University, has enabled him to hire the necessary people to launch clinical studies, such as with his AI study, and to recruit patients from the community.

"From a research perspective, the multidisciplinary environment is what attracted me to UT Southwestern,” Dr. Hajjar said. “The underlying culture of talent and collaboration needed to tackle big challenges like Alzheimer’s is already here.”

• Dr. Diamond holds the Effie Marie Cain Distinguished University Chair in Alzheimer’s Research.
• Dr. Hajjar holds the Pogue Family Distinguished University Chair in Alzheimer’s Disease Clinical Research and Care, in Memory of Maurine and David Weigers McMullan.