APP and early-onset autosomal dominant Alzheimer disease: Compelling pre-clinical (224, 225) and clinical evidence (226, 227) supports the involvement of the LC-NE system in Alzheimer's Disease (AD) via the influence of Ars (Figure 5) on the processing of amyloid precursor protein (APP) (228–230), dysregulation of the stress-signaling axis (231), and exacerbation of neuroinflammation (144).