Altered locus coeruleus links to atrophy and hypometabolism in individuals with high Alzheimer's disease biomarkers

INTRODUCTION: The locus coeruleus (LC), the first region to contain tau pathology in Alzheimer's disease (AD), releases norepinephrine, which has a neuroprotective role. We examined whether LC integrity relates to whole-brain integrity and how AD biomarkers may moderate this relationship. METHODS: LC intensity and volume were estimated using automatic segmentation on neuromelanin-sensitive magnetic resonance imaging acquired in n = 71 cognitively unimpaired elderly from the Age-Well randomized controlled trial. We investigated the associations between LC integrity and whole-brain gray matter volume (GMV) and glucose metabolism, as well as the interactions with amyloid positron emission tomography and plasma phosphorylated tau231, neurofilament light chain and glial fibrillary acidic protein. RESULTS: While only LC intensity was directly associated with GMV, both LC measures (intensity and volume) interacted positively with AD biomarkers to predict GMV and glucose metabolism. DISCUSSION: Our results support concomitant LC and gray matter alterations in the context of aging and elevated AD biomarker levels. CLINICAL TRIAL REGISTRATION: Age-Well randomized clinical trial of the Medit-Ageing European Project. TRIAL REGISTRATION NUMBER: EudraCT:2016-002,441-36; IDRCB:2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819.