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The locus coeruleus (LC), the brain’s principal noradrenergic nucleus, is among the first regions to show tau pathology in Alzheimer’s disease (AD). Its widespread projections regulate arousal, attention, sleep–wake dynamics, often disrupted early in the disease. This seminar will explore recent evidence on the degeneration of the LC across the Alzheimer’s disease continuum, integrating post-mortem, neuroimaging, and cerebrospinal fluid biomarker data. I will discuss how LC dysfunction contributes to cognitive, neuropsychiatric, and sleep alterations in AD, and how targeting this system may open novel diagnostic and therapeutic avenues.
