The involvement of insulin in Alzheimer’s can be considered the simplest possible explanation for the slow, relentless development of Alzheimer’s plaques in the aging brain. Insulin (in a test tube) will monopolize the attention of the insulin-degrading enzyme (IDE), which normally degrades and clears both amyloid proteins and insulin from around the neurons. The more insulin available in the brain, by this scenario, the less IDE is available to clean up amyloid, which then accumulates excessively and clumps into plaques. In animal experiments, the less IDE available, the greater the concentration of amyloid in the brain. Mice that lack the gene to produce IDE develop versions of both Alzheimer’s disease and Type 2 diabetes.*60

Much of the relevant research in humans on insulin and Alzheimer’s has been done by Suzanne Craft, a neuropsychiatrist at the University of Washington. In 1996, Craft and her colleagues reported that boosting insulin levels, at least in the short term, seems to enhance memory and mental prowess, even in Alzheimer’s patients. This linked insulin to the biochemical regulation of memory in the brain, but it said nothing about the long-term, chronic effects of hyperinsulinemia. In 2003, Craft reported that when insulin was infused into the veins of elderly volunteers, the amount of amyloid in their cerebral spinal fluid increased proportionately. This implied that the level of amyloid protein in their brain had increased as well. The older the patient, the greater the increase in amyloid protein. As Craft sees it, if insulin levels are chronically elevated (hyperinsulinemia), then brain neurons will be excessively stimulated to produce amyloid proteins, and IDE will be preoccupied with removing the insulin, so that less will be available to clean up the amyloid. “We’re not saying this is the mechanism for all of Alzheimer’s disease,” Craft says. But “it may have a role in a significant number of people.”

This evidence linking insulin, amyloid, and Alzheimer’s has now evolved to the point where it has “attendant therapeutic implications,” as the Harvard neurologists Dennis Selkoe and Rudolph Tanzi wrote in a 2004 article. “Compounds that subtly increase IDE activity,” they suggested, “could chronically decrease [amyloid] levels in the human brain.” This implies that anything that decreases insulin levels over the long term (and so increases the amount of IDE available to clean up amyloid)—including such dietary approaches as eating less carbohydrates—will achieve the same effect. This isn’t to say that eating carbohydrate foods to excess is a cause of Alzheimer’s, only that mechanisms have now been identified to make the hypothesis plausible.