School of Medicine

New hope for old disease

Randall J. Bateman, MD, examines Taylor Hutton, a participant in a global multicenter study testing drugs that may delay or prevent Alzheimer’s onset. An active Alzheimer’s advocate, Hutton attends and speaks at awareness events and wears an Alzheimer’s awareness tattoo on her foot. (Photo: Matt Miller)

Doctors may soon be able to predict, prevent Alzheimer’s disease

From the WashU Outlook Magazine

Caring for an aging relative with Alzheimer’s disease, watching memories slowly slip away, is an exhausting and heartbreaking ordeal. For those with the condition, modern medicine can offer little in the way of treatment as the disease inexorably strips away their ability to recognize and understand the world around them….

Step one: diagnosis

The first sign is usually forgetfulness — a forgotten conversation, a misplaced item, a question asked and answered and asked again. Until a few decades ago, such lapses might have been chalked up to the normal effects of aging. But Leonard Berg, MD, a professor of neurology at Washington University, was concerned that the distinction between normal aging and dementia was poorly understood, so in 1972 he started a faculty lunch group to discuss how to distinguish the two processes.

“At the time, there was no standard method to distinguish normal aging from very mild dementia,” said John C. Morris, MD, the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology and professor of pathology and immunology. “So Leonard and his colleagues developed a clinical tool to diagnose dementia and to determine its severity.”…

…Today, we know that memory lapses could be caused by many things: lack of sleep, medications, vitamin deficiencies, brain tumors or neurological diseases other than Alzheimer’s, such as Parkinson’s disease or frontotemporal dementia.

“When people come in and they’re clearly impaired but we don’t know what the cause is, that’s when biomarkers can be really useful,” said Anne Fagan, PhD, a professor of neurology and head of the biomarker research unit at the Knight ADRC. Biomarkers are proteins or other biomolecules that indicate the presence of disease.

Research by Fagan and others has established that two proteins linked to Alzheimer’s disease — amyloid beta and tau — can be detected in the cerebrospinal fluid that bathes the brain and spinal cord. Neurologists can resolve a difficult diagnosis by taking a spinal tap and measuring levels of the two proteins.

“I use the results of these biomarker tests to inform the care of my patients,” said Gregory S. Day, MD, an assistant professor of neurology. “A few decades ago, Alzheimer’s was formally diagnosed only on autopsy. Now using biomarkers or imaging, we can tell people what is going on very early in the process.”

Stopping the disease in its tracks

Early detection allows physicians to discuss lifestyle modifications and financial arrangements with patients. It does not, however, allow them to offer any medications to slow or stop the disease. The Food and Drug Administration has not yet approved any such drugs.

David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor, head of the Department of Neurology and professor of developmental biology, is trying to change that. He studies the basic biology underlying Alzheimer’s disease — how amyloid beta and tau build up in the brain, why clumps of such proteins cause brain cells to die, and how drugs can be designed to interrupt the process. The research of Holtzman and colleagues at Eli Lilly and Company led to the development of solanezumab, a drug designed to counter amyloid beta’s toxic effects. Solanezumab and another drug, gantenerumab, are now being evaluated in the first-ever Alzheimer’s disease prevention trial, at the School of Medicine and elsewhere…

Detecting the silent phase

…A blood test is also on the horizon. “Last year my lab reported the first highly specific blood test for amyloid,” said Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology. “Since then, other groups have replicated and expanded on it. I think we’ll see that test in use in doctors’ offices in the next three to five years.”

Rajendra S. Apte, MD, PhD, the Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences, and Gregory P. Van Stavern, MD, a professor of ophthalmology and visual sciences, recently have reported a small study that suggests that signs of Alzheimer’s might be detectable through a specialized, noninvasive eye exam.

  Read more in the Outlook Magazine.