Chemical ablation of locus coeruleus terminals in mice dysregulates behavioral features reminiscent of prodromal Alzheimer’s disease

The prodromal stages of Alzheimer’s disease (AD), which precede cognitive impairment by decades, are characterized by neuropsychiatric symptoms such as anxiety, agitation, impulsivity, and sleep disturbances that significantly impair quality of life. The brainstem noradrenergic locus coeruleus (LC) modulates behaviors that are reminiscent of these prodromal symptoms. Furthermore, the loss of norepinephrine (NE) terminals in LC‐projecting regions is a prominent feature of early AD, implicating LC dysfunction as a possible contributor to prodromal symptoms. However, the behavioral and pathological consequences of LC terminal loss have not been fully investigated.