The neuroanatomical features of the locus coeruleus in neurodegeneration

The pontine nucleus Locus Coeruleus (LC) is part of the so-called isodendritic core of the brain stem reticular formation and is the main source of noradrenaline in the brain. LC is placed in the upper part of the pons, and is mainly formed by medium-sized neurons containing neuromelanin. Each one of two symmetrical LC nuclei is formed by up to 60.000 neurons in humans, which send axons profusely branching and innervating the entire cerebral and cerebellar cortices. By releasing noradrenaline through “bouton en passage” it modulates the activity of several cortical areas. In particular, LC modulates electroencephalogram activity, sleep/wake cycle, memory consolidation, and other cognitive functions, mainly related to attention, alerting and novelty orienting. A significant LC cell loss has been shown in Parkinson’s Disease (PD) and in cases of severe Alzheimer’s Disease (AD) dementia, in post-mortem studies. Exciting histological data suggest a very early involvement of LC in the pathogenesis of AD: accumulation of phospho-tau deposits in the axons of LC neurons seems to precede their occurrence in limbic regions in Mild Cognitive Impairment (MCI, the prodromal phase of Dementia) or even in pre-MCI stages. LC impairment seems to accelerate beta amyloid plaques deposition and neuroinflammation. Recently, specific 1,5 and 3,0 Tesla Magnetic Resonance Imaging (MRI) protocols and post-processing analysis have been developed in order to detect neuromelanin-containing LC neurons in vivo in controls and in PD patients. In the presentation, after introducing the state of the art of the neuroanatomical features of LC in degenerative diseases, we report existing data on the MRI characterization of LC in PD and controls, as well as more recent evidences in AD and MCI. The potential role of these MRI data in helping to disclose the pathogenesis and contributing to the correct diagnosis in patients is discussed.