The role of the locus coeruleus/norepinephrine system in the pathogenesis of neurodegenerative disorders: An update

Purpose of review The aim of this review was to provide an update on current and emerging knowledge of the neuropathological processes affecting the locus coeruleus/norepinephrine (LC/NE) system, their effect on Alzheimer's disease and Parkinson's disease symptomatology, including efforts to translate these notions into therapeutic actions targeting the noradrenergic system. Recent findings Over the past 2 years, work from multiple groups has contributed to support an early role of locus coeruleus degeneration and/or hyperactivation in the neurodegenerative process, including a trigger of neuroinflammation. Imaging advances are allowing the quantification of locus coeruleus structural features in vivo, which is critical in the early stages of disease. Nonmotor and noncognitive symptoms, often secondary to the involvement of the LC/NE system, are becoming more important in the definition of these diseases and their treatment. The diverse symptomatology of Parkinson's disease and Alzheimer's disease, which is not limited to cardinal motor and cognitive abnormalities, strongly suggests a multisystem neurodegenerative process. In this context, it is increasingly clear how the LC/NE system plays a key role in the initiation and maintenance of the neurodegenerative process.