New research by David Holtzman, M.D. at the Washington University School of Medicine points to a sleep regulation protein in the brain as a possible target for Alzheimer's disease treatment or prevention. The protein, called orexin, plays a role in rousing the brain from sleep.
It has been known for some time that there is a correlation between sleep problems and Alzheimer's disease, in both animal models and human patients. Now, Holtzman and colleagues have gotten closer to understanding that correlation. The researchers found that Alzheimer's mice who lacked the gene for orexin developed far less amyloid plaques (a hallmark of Alzheimer's pathology) than mice with the gene. Furthermore, mice with an elevated level of orexin developed even more amyloid plaques.
While this research shows much promise for development of an Alzheimer's therapeutic targeted at lowering orexin levels, Holtzman cautions that "we will have to think carefully about how to target it". When scientists attempted to lower orexin levels in mice without changing sleep patterns, this had no effect on the development of amyloid plaques. This indicates that it may be difficult to treat Alzheimer's via orexin without also affecting patients' sleep. Still, Holtzman is optimistic about orexin as a target. "The declines in plaque levels that we saw in the mice were very strong," he says, "so we're still very interested in exploring its potential for reducing risk." Holtzman and colleagues plan to study Belsomra, an orexin-regulating sleep medication recently approved by the FDA, for its effects on amyloid production and accumulation.
David Holtzman serves on the Cure Alzheimer's Fund Research Consortium. This study was supported in part by a grant from Cure Alzheimer's Fund.
Read more about the orexin study here.