News Release

Researchers get closer to preventing Alzheimer's disease

Peer-Reviewed Publication

The Mount Sinai Hospital / Mount Sinai School of Medicine

(New York, New York, July 6, 2006) – A recent study directed by Mount Sinai School of Medicine identifies a faulty molecule in the brain found in cases of mild cognitive impairment (MCI). Researchers say this faulty molecule may be responsible for the progression of MCI to mild Alzheimer's disease (AD) dementia. The study, which appeared June 10th online in the journal Neurobiology of Aging, may lead to preventative treatments for AD.

An estimated 4.5 million Americans have Alzheimer's disease and presently there are no known cures or effective preventive strategies.

"Alzheimer's Disease is a growing health concern that affects millions of people, "says Giulio Maria Pasinetti, M.D., Ph.D., Professor of Psychiatry and Neuroscience, Director of the Neuroinflammation Research Center at Mount Sinai School of Medicine and lead author of the study. "We hope our research provides direction for preventative treatments to delay the onset of AD dementia by eliminating amyloid plaque-causing peptides in the brain."

People with AD exhibit elevated levels of beta-amyloid peptides that cause plaque buildup in the brain (the main characteristic of AD). In the earliest stages of Alzheimer's, beta-amyloid peptides are on the rise, especially in the two connected brain regions critical for memory functions-- the hippocampus and entorhinal cortex.

In this study, Dr. Pasinetti and colleagues at Mount Sinai School of Medicine in New York suggests one reason for that early increase of beta-amyloid peptides: an enzyme that breaks down beta-amyloid peptides, also referred to as an insulin-degrading enzyme (IDE), is not active in the brain in the cases at high-risk for developing AD. To assess possible changes in IDE during MCI, the investigators measured protein levels and enzymatic activity in postmortem brain tissue from 46 elderly subjects.

Implications

A loss of IDE activity has been previously shown to occur in severe AD dementia, and the current results raise the possibility that a deficit in degradation of amyloid peptides from IDE could raise levels of toxic beta-amyloid peptides even before AD dementia is diagnosed. If these results are confirmed, Mount Sinai researchers suggest that boosting IDE activity pharmacologically may reverse beta-amyloid peptide accumulation. This new finding may provide a pharmacological therapeutic angle to preventing AD dementia.

Dr. Pasinetti and colleagues also measured levels of beta-amyloid peptides in the entorhinal cortex and found that the amount of beta-amyloid was inversely correlated with IDE activity they measured in the hippocampus. These results support the idea that alterations in IDE might be causally related to beta-amyloid peptides accumulation, starting in the earliest stages of AD.

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Mount Sinai School of Medicine

Located in Manhattan, Mount Sinai School of Medicine is internationally recognized for ground-breaking clinical and basic-science research, and innovative approaches to medical education. Through the Mount Sinai Graduate School of Biological Sciences, Mount Sinai trains biomedical researchers with an emphasis on the rapid translation of discoveries of basic research into new techniques for fighting disease. One indication of Mount Sinai's leadership in scientific investigation is its receipt during fiscal year 2005 of $174.1 million in research support from the NIH. Mount Sinai School of Medicine also is known for unique educational programs such as the Humanities in Medicine program, which creates opportunities for liberal arts students to pursue medical school, and instructional innovations like The Morchand Center, the nation's largest program teaching students and physicians with "standardized patients" to become not only highly skilled, but compassionate caregivers. Long dedicated to improving its community, the School extends its boundaries to work with East Harlem and surrounding communities to provide access to health care and educational programs to at risk populations.


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