Although Parkinson's disease (PD) is becoming increasingly important in ageing societies, its diagnosis still relies on the presence of classical motor symptoms that usually manifest in the later stages of the disease's progression. Patients may, however, present non-motor signs as cognitive and/or mood issues years prior to the onset of the motor ones. The Locus Coeruleus (LC) is one of the first areas to exhibit Lewy bodies and neurodegeneration. Its dysfunction is associated to the appearance of nonmotor symptoms due to its noradrenergic (NA) projections and influence on the homeostasis of dopaminergic (DA) networks. We have set up a prodromal mouse model of human alpha-synuclein (α-syn) overexpression at the LC by viral vector stereotaxic injections. Our goal is to characterize behavioural, functional, and structural changes driven by dysregulation of the LC-NA system, locally and in projecting areas such as the hippocampus or prefrontal cortex. Thus, we have studied behavioural phenotypes finding affectations related to spatial and working memories. Moreover, we have analysed structural changes in local inflammatory-related cells, as astrocytes and microglia, together with alterations in NA fiber network. These data, along with preliminary functional studies, provide an insight into how LC-NA dysregulation occurs at very early phases of PD and may aid in the search for early markers to facilitate its diagnosis.