As we recognize Alzheimer’s Awareness month, we are reminded of the hardships faced in the wake of the disease. Today, tremendous progress is being made in order to eradicate this devastating illness, and we share this update to inspire hope.

Alzheimer’s disease, a progressive, irreversible brain disorder that destroys memory and other vital mental functions, has touched the lives of families everywhere. Today, more than 5 million Americans are now afflicted, and that number is expected to reach nearly 14 million by 2050.

For years, scientists and researchers have searched for answers to better understand root causes of Alzheimer’s. It has proved one of the most elusive mysteries of the brain, and while advances in treatment help afflicted patients, we don’t yet have a cure.

Now, a cure for Alzheimer’s may be possible within our lifetimes.

A team at UT Southwestern Medical Center’s Peter O’Donnell Jr. Brain Institute, led by Marc Diamond, M.D., is conducting groundbreaking research to uncover the mechanisms that underlie this disease so that we can pinpoint how and why neurodegeneration begins, and why it progresses. The answers to these questions are providing important clues for therapy.

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Understanding Tau

It has long been recognized that the tau protein underlies dementia in Alzheimer’s. Dr. Diamond is credited with describing the cellular events that underlie progression of the disease: how pathology can begin in one area and spread throughout the brain. In fact, in many respects tau acts like an infectious agent, similar to the protein that causes mad cow disease. Recent breakthroughs from Dr. Diamond’s lab have revealed the origins tau pathology at the level of the three dimensional structure of the protein itself. Dr. Diamond’s team has discovered that tau protein adopts multiple possible shapes, each associated with a different form of dementia. This is now changing how new approaches to therapy and diagnosis are being developed at the Center for Alzheimer’s and Neurodegenerative Diseases.

 

Video courtesy of Center Times, the official Newsroom of UT Southwestern Medical Center.

 

Transforming Therapy

A study from the O’Donnell Brain Institute provided novel insight into the shape-shifting nature of the tau protein. The revelation offers new strategies to detect the devastating disease before it takes hold, stopping it before symptoms of memory loss or cognitive decline can manifest. This work, published in two papers in eLife (Mirbaha et al., Sharma et al.) contradicts the previous belief that an isolated tau protein has no distinct shape and is only harmful after it begins to assemble with other tau proteins to form the distinct tangles seen in the brains of Alzheimer’s patients.

Instead, Dr. Diamond’s lab found that a shape shift within an isolated tau protein holds the key to myriad diseases. This is based on exposure of normally hidden sequences that allow the tau protein to stick to itself, enabling the formation of tangles that kill neurons. With this new knowledge, the lab is now embarking on discovery of small molecules that will stabilize the normal (harmless) form of tau, and vaccines that will enable the immune system to target disease-causing forms.

In fact, studies from the lab have already contributed to the development of an anti-tau antibody that is in clinical trials. This antibody binds tau, and may facilitate its clearance from the brain.

Revolutionary advances like these continue in part thanks to the support of visionary donors. The passion of researchers like Dr. Diamond and the generosity of those who support innovation in medicine have brought us one hopeful step closer to finding a cure for Alzheimer’s.