11.01.2006

Caloric Restriction may Prevent Alzheimer's
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A new suggests that certain dietary regimens might slow or even reverse symptoms of Alzheimer's disease.

The study, which is published in the Journal of Biological Chemistry, is the first to show that restricting caloric intake, and specifically carbohydrates, may prevent Alzheimer's disease 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," said Giulio Maria Pasinetti, 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."

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 Alzheimer's disease cases, the most common form of Alzheimer's disease.

People with Alzheimer's disease exhibit elevated levels of beta-amyloid peptides that cause plaque buildup in the brain. 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.

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 Alzheimer's disease amyloid neuropathology.

Since alpha-secretase is known also to inhibit the generation of beta-amyloid peptides in the Alzheimer's disease affected brain, the study demonstrates a mechanism by which dietary caloric restriction might benefit Alzheimer's disease. The study also finds that a high caloric intake based on saturated fat promotes Alzheimer's disease type beta-amyloidosis, while caloric restriction based on reduced carbohydrate intake seems predisposed to prevent it.



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