In studies of transgenic mice, Dr Bredesen and colleagues found that beta-amyloid precursor protein (APP) signaling can be manipulated to inhibit the underlying pathophysiology that causes AD.
However, many different metabolic factors contribute to APP signaling, including hormones, inflammatory mediators, and exercise.
This suggests that the pathobiology of AD must be approached at different points of intervention and not with a single targeted agent.
“Just as for other chronic illnesses such as atherosclerotic cardiovascular disease, the goal is not simply to normalize metabolic parameters, but rather to optimize them,” the investigators write.
“Based on the hypothesis that AD results from an imbalance in an extensive plasticity network, the therapy should address as many network components as possible, with the idea that a combination approach may create an effect that is more than the sum of the effects of many monotherapeutics,” the researchers add.
Critical to the success of this hypothesis is the idea that there is a “threshold” at which multiple interventions will start to reverse the pathology leading to memory loss.
As Dr Bredesen points out, it has been shown by Dean Ornish, MD, founder and president of Preventive Medicine Research Institute, San Francisco, California, among others that with a large enough lifestyle change, buildup of atherosclerotic plaque and subsequent coronary artery disease can be reversed.
Similarly, in AD, if enough of the factors that contribute to the imbalance between synaptoblastic and synaptoclastic signaling in the brain can be reversed, deficits in the network that lead to memory loss can be redressed — “and you start to see improvement, which is exactly what we saw in these patients. If they follow enough of these interventions, they are able to improve,” Dr Bredesen said.