Ketone Bodies as a Therapeutic for Alzheimer's Disease
Alzheimer's disease (AD) is characterized by progressive declines in the cerebral metabolic rate of glucose (CMRglc) in regions of the brain associated with baseline activity. Low CMRglc occurs early in the disease and may represent a target for therapeutic intervention. One promising means to address low CMRglc is the induction of ketosis. Ketosis is a metabolic state characterized by an increase in circulating ketone bodies. Ketone bodies (β-hydroxybutyrate, acetoacetate and acetone) are substances naturally produced by the body from fat stores under conditions of low glucose availability. Ketone bodies serve a critical role in substituting for glucose in conditions such as extended fasting. In addition, ketone bodies have demonstrated neuroprotective properties in animal models of several neurodegenerative conditions. Ketosis can be achieved by adherence to a low carbohydrate ketogenic diet or through consumption of medium chain triglycerides. Induction of ketosis by a ketogenic diet in a mouse model of Alzheimer's disease reduced Aβ40 and 42 levels by 25% after 43 days on diet. Induction of ketosis by feeding medium chain triglycerides to subjects with mild to moderate AD improved cognitive performance after both acute and chronic dosing. Addressing low CMRglc by induction of ketosis represents a promising area of research in AD therapeutics.