Calorie restriction may prevent Alzheimer's through promotion of longevity program in the brain

For the first time researchers show how restricting caloric intake triggers activity in the brain associated with longevity

New York, New York A recent study directed by Mount Sinai School of Medicine suggests that experimental dietary regimens might calm or even reverse symptoms of Alzheimer's Disease (AD). The study, which appears in the July 2006 issue of the Journal of Biological Chemistry, is the first to show that restricting caloric intake, specifically carbohydrates, may prevent AD by triggering activity in the brain associated with longevity.

"Both clinical and epidemiological evidence suggests that modification of lifestyle factors such as nutrition may prove crucial to Alzheimer's Disease management," 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. "This research, however, is the first to show a connection between nutrition and Alzheimer's Disease neuropathy by defining mechanistic pathways in the brain and scrutinizing biochemical functions. We hope these findings further unlock the mystery of Alzheimer's and bring hope to the millions of Americans suffering from this disease."

Alzheimer's Disease is a rapidly growing public health concern with potentially devastating effects. An estimated 4.5 million Americans have Alzheimer's Disease and the number of Americans with Alzheimer's has more than doubled since 1980. Presently, there are no known cures or effective preventive strategies. While genetic factors are relevant in early-onset cases, they appear to play less of a role in late-onset-sporadic AD cases, the most common form of AD.

Longevity Program 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). Beta-amyloid peptides activate SIRT1, a member of a broad family of proteins known as sirtuins which influence a variety of functions including metabolism and aging.

Dr. Pasinetti and colleagues used an experimental mouse model to demonstrate that beta-amyloid peptides in the brain can be reduced by subjecting the mice to dietary caloric restriction, primarily based on low carbohydrate food. Conversely, a high caloric intake based on saturated fat was shown to increase levels of beta-amyloid peptides.

This study is the first to suggest that caloric restriction through promotion of SIRT1 (a molecule associated with brain longevity) may initiate a cascade of events like the activation of alpha-secretase which can prevent AD amyloid neuropathology. Since alpha-secretase is known also to inhibit the generation of beta-amyloid peptides in the AD affected brain, the study demonstrates a mechanism by which dietary caloric restriction might benefit AD. Most remarkably, the study finds that a high caloric intake based on saturated fat promotes AD type beta-amyloidosis, while caloric restriction based on reduced carbohydrate intake is able to prevent it.

Implications
Among lifestyle factors influencing AD, recent studies strongly support the evidence that caloric intake may play a role in the relative risk for AD clinical dementia. Most importantly, as mechanistic pathways are defined and their biochemical functions scrutinized, the evidence supporting a direct link between nutrition and AD neuropathology continues to grow.

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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.


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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