APOE and Alzheimer disease: As discussed below, higher spatial resolution fMRI studies should begin to answer to which degree LC connectivity correlates with early disease biomarkers such as APOE4 (Um et al., 2024) as well as symptomatic ramifications of AD, as has already been demonstrated for the role of the LC in depressive symptoms (Dai et al., 2023) and agitation (Liu et al., 2025) in AD, and in ageing more generally (Jacobs et al., 2018; Mijalkov et al., 2025; Vereb et al., 2023).