Reduced calorie and carbohydrate diet slows progression of Alzheimer's disease in mouse model

Researchers found that a low carbohydrate diet that reduced total caloric intake by 30% prevented the development of a fundamental feature of Alzheimer's disease (AD) in a strain of mice genetically engineered to develop the disease. The diet eliminated amyloid plaque development, which is the underlying pathology in AD. The study, published in the January issue of The FASEB Journal, is the first to demonstrate that a change in diet can slow and possibly prevent Alzheimer's diseases.

"While it is far too early for us to make specific recommendations for human diets," said Giulio Maria Pasinetti, MD, PhD, Professor of Psychiatry, Neurosciences and Geriatrics and Adult Development at Mount Sinai School of Medicine and primary investigator on the study, "these findings provide the first solid evidence that dietary changes may provide a new approach to treatment and prevention of this devastating disease."

Dr. Pasinetti and his colleagues found that mice did not develop the physiological markers of the disease when they were fed a reduced carbohydrate diet that provided 70% of the calories eaten by similar mice who were allowed to eat ad-libitum. The strain of mice used in the study was genetically engineered to produce what are known as amyloidogenic ?-amyloid peptides in the brain, resulting in formation of amyloid plaques which are known to be the fundamental problem in Alzheimer' disease. Of the mice fed ad-libitum, 100% developed these plaques. No plaque development was detected in the mice fed a carbohydrate and calorie restricted diet.

The diet regimen was begun when the mice were 3-months old, which is considered young adult and is prior to the age at when this Alzheimer's disease mouse model begins to develop plaques in the brain. The presence of plaques was evaluated at 12 months of age, which is an age at which plaques are known to be well developed in this strain.

The investigators found that anti-amyloidogenic activities were increased in mice fed the restricted diet. In other words, the calorie restricted diet activated pathways that break down amyloidogenic ?-amyloid peptides in the brain before they form the plaques characteristic of AD.

"Since the diet only reduced calories by 30%, (based on carbohydrate) the mice developed normally," said Dr. Pasinetti. "While they did not gain weight like the mice in the control group, they did not loose weight either and remained within the boundaries considered a healthy weight. Nonetheless, this rather mild change in diet resulted in a remarkable measure of disease prevention. There is epidemiological evidence that humans who consume reduced calorie diets have a lower incidence of AD. Our investigation provides a possible rational for this observation and possible mechanisms through which caloric reduction may provide protection in Alzheimer's disease."

Ongoing studies are investigating whether or not the prevention of plaque development in these mice also prevents behavioral decline and clinical studies are currently being designed at Mount Sinai School of Medicine to explore the applicability of this experimental evidence in Alzheimer's disease cases.

From Mount Sinai Hospital

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January 12, 2005