WUSTL to lead new international Alzheimer's disease research network

July 22, 2008 -- The Alzheimer's Disease Research Center (ADRC) at Washington University School of Medicine in St. Louis will lead a six-year, $16 million international research collaboration dedicated to understanding inherited forms of Alzheimer's disease. The National Institute on Aging (NIA) 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," says DIAN principal investigator John C. Morris, M.D., the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology 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 the DIAN."

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

DIAN is modeled after the Adult-Children Study at the ADRC. That study 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 them to identify telltale changes in the central nervous system decades before the symptoms of Alzheimer's disease become apparent.

"The Adult-Children Study is another genetic investigation, but it's focused on less overtly inherited forms of the disease," says Morris. "If a parent develops Alzheimer's disease at a relatively young age in a family with no known mutation that causes the disease, a genetic factor that we have yet to identify may be present, and this can notably increase the risk to the children."

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 down into a patient's 50s, 40s or even 30s. Researchers believe 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.