Drug Discovery

Cognitive Enhancement

Noradrenergic treatments for Alzheimer's disease

Investigator(s): David Weinshenker, Ph.D.

Institution(s): Emory University

Duration:

Summary:

Cholinergic deficits observed in AD have lead to the development of currently marketed drugs called cholinesterase inhibitors such as Aricept. Another underappreciated feature of AD is the degeneration of the locus coeruleus (LC), which results in loss of norepinephrine (NE) input to brain areas that are affected in AD. Weinshenker has recently found that LC lesions exacerbate inflammation, plaque load, neuronal loss, and certain forms of learning and memory in mice overexpressing mutant beta-amyloid, a commonly used model of AD. These results indicate that loss of noradrenergic neurons may significantly contribute to AD pathology and symptomology. The goal of this proposal is to determine whether pharmacological enhancement of NE can be useful in AD. If demonstrated, this may result in novel and effective new treatments for AD.