Abstract
It has been shown that caloric restriction (CR) delays aging
and possibly delays the development of Alzheimer's disease (AD). We conjecture
that the mechanism may involve interoceptive cues, rather than reduced energy
intake per se. We determined that hunger alone, induced by a ghrelin agonist,
reduces AD pathology and improves cognition in the APP-SwDI mouse model of AD.
Long-term treatment with a ghrelin agonist was sufficient to improve the
performance in the water maze. The treatment also reduced levels of amyloid
beta (Aβ) and inflammation (microglial activation) at 6 months of age compared
to the control group, similar to the effect of CR. Thus, a hunger-inducing drug
attenuates AD pathology, in the absence of CR, and the neuroendocrine aspects
of hunger also prevent age-related cognitive decline.