Buck Institute Study Shows Birth of New Nerve Cells Increased in Mice with Familial Alzheimer's Disease

Neurogenesis Linked More Closely with Alzheimer’s Disease; Animal Model Provides Basis for Studying How Neurological Diseases Stimulate Nerve Growth

August 30, 2004 Mice with an inherited form of Alzheimer’s disease (AD) may try to heal their damaged brains by growing new nerve cells, even before they develop amyloid plaques that are a hallmark symptom of the disease, according to a new Buck Institute study.

While nerve cell birth, also called neurogenesis, has been identified in brain tissue taken from humans suffering from AD, these animal studies, due to be published the week of September 7th  in the on-line edition of the Proceedings of the National Academy of Sciences (PNAS),  imply that the nerve growth is a direct result of  AD. The human tissue likely came from individuals who had been treated for AD and/or other conditions; the mice provide a more “pure” model because they have never received medications, have no additional diseases and are not malnourished.

The mice used in this study were bred to develop two symptoms of AD -- amyloid plaques and abnormal communication between nerve cells -- but not to lose nerve cells, another feature of the disease.  David Greenberg, MD, PhD, lead scientist of the study, noted that the mice showed signs of increased nerve growth at three months of age, well before they developed amyloid plaques. “The animals reacted sooner than one might expect,” said Greenberg, “We thought that the loss of nerve cells might spur the growth of new ones, but these animals never lost nerve cells. These findings lead us to believe that neurogenesis is triggered by more subtle disease manifestations.”

Greenberg said researchers will now focus on looking at mice genetically engineered to have single manifestations of the disease, either amyloid plaques or abnormal communication between nerve cells, allowing them to identify the actual mechanism that triggers the early birth of new nerve cells.

The Buck Institute was the first to identify increased birth of new nerve cells in humans with AD in a study published late last year. That study and this most recent work involved collaboration between two laboratories at the Buck Institute, Greenberg’s lab which is focused on stroke, and the lab of Institute President Dale Bredesen, MD, which focuses on AD.  “This study provides more hope that treatments can be developed that will help forestall AD well before symptoms ever appear,” said Bredesen. “In addition to saving patients and families untold grief, preventive treatments would greatly impact our health care system, which spends about $100 billion a year dealing with the disease."

Approximately 4.5 million Americans are affected by AD, which usually starts with mild memory problems and ends with severe brain damage; it is the most common form of dementia in older people. The exact cause of AD is undetermined and no cure has been discovered.  AD usually begins after the age of 60 with patients commonly living for eight to ten years after diagnosis.

Joining Greenberg and Bredesen as co-authors of the paper are Buck Institute scientists Kunlin Jin, MD, PhD; Veronica Galvin, PhD; Lin Xie, BS;  and Xiao Ou Mao, MD. .  The work was supported by the National Institutes of Health, U.S. Public Health Service Grants and by a grant from the John D. French Alzheimer’s Foundation.

The Buck Institute is the only freestanding institute in the United States that is devoted solely to basic research on aging and age-associated disease. The Institute is an independent non-profit organization dedicated to extending the healthspan, the healthy years of each individual’s life.  Buck Institute scientists work in an innovative, interdisciplinary setting to understand the mechanisms of aging and to discover new ways of detecting, preventing and treating conditions such as Alzheimer’s and Parkinson’s disease, cancer and stroke.  Collaborative research at the Institute is supported by new developments in genomics, proteomics and bioinformatics technology.

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