The Role of the Locus Coeruleus in Alzheimer’s Disease: An Insightful Conversation with Dr. Cassidy

Alzheimer’s disease (AD) is a multifaceted neurological condition characterized by a variety of clinical and pathophysiological markers. Among the critical components under investigation is the locus coeruleus (LC), a small nucleus in the brainstem whose degeneration has been linked to AD. However, our understanding of the relationship between LC integrity and the stages of AD remains limited. In this episode, we are joined by Dr. Cassidy, whose pioneering research uses neuromelanin-sensitive MRI (NM-MRI) to examine the role of the LC-norepinephrine system in AD. The study involved cognitively normal older adults, individuals with mild cognitive impairment (MCI), and AD patients. The researchers assessed the LC-norepinephrine system's integrity based on the contrast-to-noise ratio of the LC on NM-MRI images. Dr. Cassidy and his team found that LC signal contrast decreased in tau-positive participants and negatively correlated with the Braak stage, a measure of tau pathology progression in AD. Remarkably, higher LC signal predicted the severity of neuropsychiatric symptoms (NPS), particularly impulse control symptoms, independent of tau burden, amyloid-β burden, and cortical gray matter volume.Join us as we dive deep into these intriguing findings with Dr. Cassidy. We'll discuss how NM-MRI could serve as a practical biomarker, potentially predicting the risk of NPS or guiding their treatment in AD, and explore the implications of LC preservation in AD progression.Keywords: Alzheimer’s disease, Locus coeruleus, Neuromelanin-sensitive MRI, Tau protein, Amyloid-β, Neuropsychiatric symptoms, Dr. Cassidy.Cassidy, C.M., et al. Association of locus coeruleus integrity with Braak stage and neuropsychiatric symptom severity in Alzheimer’s disease. https://doi.org/10.1038/s41386-022-01293-6