School to lead international Alzheimer’s disease research network

The Alzheimer’s Disease Research Center (ADRC) at the School of Medicine will lead a six-year, $16 million international research collaboration dedicated to understanding inherited forms of Alzheimer’s disease. The National Institute on Aging will fund the project.

Forms of Alzheimer’s disease linked to inherited mutations are rare but have provided scientists with many important insights into the more common “sporadic” forms of the disease. Because individuals with these inherited forms of Alzheimer’s are widely dispersed geographically, there have been too few at any one center to conduct extensive research. Through the newly created Dominantly Inherited Alzheimer’s Network (DIAN), investigators hope to organize and enroll a broad pool of qualified volunteers.

“For treatments now in development to be optimally beneficial for patients, we have to find ways of diagnosing Alzheimer’s disease as early as possible,” said John C. Morris, M.D., the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology, principal investigator of DIAN and director of the ADRC. “That’s likely to happen much more quickly as we move from studying the few family members in St. Louis with inherited Alzheimer’s to the 300 family members who will be accessible through DIAN,” he said.

DIAN includes WUSTL; a consortium involving Harvard University, Massachusetts General Hospital and Brown University; Columbia University; Indiana University; the University of California, Los Angeles; the University College London’s Institute of Neurology, Queen Square; and a consortium of the universities of Brisbane, Perth and Sydney in Australia.

DIAN is modeled after the ADRC’s Adult-Children Study, which regularly conducts detailed physical and mental assessments of healthy, middle-aged children whose parents have been diagnosed with Alzheimer’s. Researchers hope this will help identify telltale changes in the central nervous system decades before the symptoms of Alzheimer’s disease become apparent.

Scientists are aware of inherited mutations in three genes that can cause Alzheimer’s disease: amyloid precursor protein, presenilin 1 and presenilin 2. Changes in all three genes cause Alzheimer’s to develop early, potentially pushing the age of onset into a patient’s 50s, 40s or even 30s. Researchers say all the mutations lead to increased production of amyloid beta 42, a protein fragment that is the principal ingredient of brain plaques found in Alzheimer’s patients. This has made amyloid beta a primary target for researchers developing new drugs for Alzheimer’s disease.

Scientists already have several potential indicators, known as biomarkers, of the early onset of Alzheimer’s disease. However, the only current way to confirm their validity is to wait years or decades and see whether volunteers who have the biomarkers eventually get the disease. DIAN may help scientists shorten this process dramatically by allowing them to look for the potential biomarkers in individuals who have inherited a known mutation from an affected parent and are almost certain to develop the disease.

To get important clues about how and why the disease develops, scientists plan to closely monitor possible biomarkers in DIAN volunteers age 21 and older.

“The most exciting aspect of DIAN is that we have a chance to determine the type and order of brain changes that herald the onset of dementia in years to come,” Morris said. “If we’re going to develop preventive therapies, we have to know when to target each of the mechanisms in the brain that may be contributing to the beginnings of Alzheimer’s disease.”