Can LC structural and functional changes serve as a biomarker for Alzheimer’s diseaseA systematic review

Alzheimer’s Disease (AD) is a chronic and progressive neurodegenerative disorder and the most common cause of dementia in older adults. It is characterized by gradual memory loss, cognitive dysfunction, and neuropathological hallmarks including extracellular amyloid-β plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. Recently, the Locus Coeruleus (LC)—a small brainstem nucleus and the principal source of norepinephrine in the brain—has been identified as one of the earliest sites of AD-related pathology. The LC plays critical roles in arousal, attention, memory consolidation, and sleep–wake regulation. Histopathological studies suggest that LC degeneration may precede cortical involvement and trigger downstream neurodegenerative processes. Advances in neuroimaging techniques, including neuromelanin-sensitive MRI (NM-MRI), positron emission tomography (PET), resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI), now enable in vivo assessment of LC structural and functional integrity. This systematic review aims to evaluate existing evidence of LC alterations across AD, Mild Cognitive Impairment (MCI), and healthy controls (HC), and to explore its potential as a diagnostic or prognostic biomarker.