In 2017, Dr. Rudy Tanzi proposed the acronym “SHIELD” as a mnemonic for lifestyle strategies against Alzheimer’s disease (AD). S denoted the importance of sleep. H represented the need to “handle the stress.” I represented the importance of social interactions. E denoted the need for exercise. L represented the need to constantly learn in order to maintain brain plasticity. And D reminded us of the importance of a healthy diet.

Our first CureAlz project investigated the E. We discovered that genes in blood vessels from an AD brain were perturbed, and exercise may partly rescue these defects. This was important because the majority of AD patients also suffer from vascular problems. So, the importance of the E in SHIELD may be partly related to its ability to rescue blood vessels in the AD brain.

In this renewal project, we will focus on the interactions between the “E for exercise” and the very first and arguably most important yet underappreciated letter in the SHIELD acronym—S for sleep. Sleep-wake cycles are part of a fundamental biological mechanism called the circadian rhythm. It is now recognized that disruptions in circadian rhythms may be an important part of AD. In this new project, we will build on discoveries from our previous funding cycle. We will test the idea that gene expression in blood vessels and inflammatory cells within the brain also have their own circadian rhythms, but these rhythms are disrupted in AD. Using exercise as a probe, we hope to find ways to renormalize these circadian rhythms, thus rescuing function in the AD brain.