Deterioration and loss of the microscopic connections between brain cells (referred to as synapses) underlies the memory loss and other mental dysfunction seen in Alzheimer disease. The culprit behind all of this damage and destruction is believed to be soluble beta amyloid fibrils. They bind to specific sites on nerve cell membranes (the outer coatings of the nerve cells) in the region of synaptic connections. In so doing, they trigger the production of inflammation and subsequent damage to the tiny nerve cell connections. As they are lost, the nerve cells become functionally disconnected and can't perform the computer-like computations that are the basis for every thought we have.

This information is not particularly new. However, the observation that a protective mechanism exists that can shield nerve cells from the beta amyloid toxins is. The exciting thing about this finding is that it can prevent the deleterious changes from happening before symptoms develop! The savior in all of this drama is the hormone insulin. It so happens that insulin in the brain prevents the binding of beta amyloid fibrils to the receptors they must interact with to cause damage to the synaptic connections.

The proposed mechanism behind the insulin protective effect is not one of insulin interfering with the binding of beta amyloid to its receptors, but the actual down-regulation, or reduction , in the number of beta amyloid binding sites on the nerve cell membranes. To cause this reduction in beta amyloid binding sites, insulin must first bind to insulin receptors on the same nerve cell and produce an insulin signal within the nerve cell. The end result of this complex process is the loss of beta amyloid binding sites in the synaptic region. Without the binding sites, beta amyloid is almost helpless.

The novel finding that insulin mitigates synaptic vulnerability suggests that mechanisms that enhance brain insulin signaling, which declines with aging and diabetes, could potentially slow the onset or development of Alzheimer disease. In brain cells grown in tissue culture (like growing bacteria in a Petrie dish), this observation was confirmed in two separate ways -- by directly adding insulin to nerve cells, and by adding a drug that improves insulin sensitivity (meaning when the insulin that was normally present binds to its receptor of the nerve cells, the response is enhanced). Both interventions improved insulin signaling and decreased inflammation and loss of synapses.

While these studies were done in tissue culture, there are other ways to enhance brain insulin signaling, which include calorie and carbohydrate restriction. These interventions were studied in mice who were placed on low calorie/low carb diets. The lead author in this study was Dr. Giulio Maria Pasinetti. Based on his findings, he noted, "Both clinical and epidemiological evidence suggest that modification of lifestyle factors such as nutrition may prove crucial to Alzheimer's disease management. 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."