Disrupted functional connectivity of the locus coeruleus in healthy adults with parental history of Alzheimer's disease

Prevention and early treatment strategies for Alzheimer's disease (AD) are hampered by the lack of research biomarkers. Neuropathological changes in the Locus Coeruleus (LC) are detected early in AD, and noradrenaline plays a neuroprotective role in LC projecting areas. We assessed functional connectivity (FC) of the brainstem in asymptomatic individuals at familial risk for AD hypothesizing that FC of the LC will be decreased in relation to not-at-risk individuals. Thirty-one offspring of patients with late-onset AD (O-LOAD) (22 females; mean age ± SD = 50.36 ± 8.32) and 28 healthy controls (HC) (20 females; mean age ± SD = 53.90 ± 8.44) underwent a neurocognitive evaluation and a resting-state functional magnetic resonance imaging acquisition. In FC analyses we evaluated whole-brain global connectivity of the brainstem area, and subsequently assessed seed-to-voxel FC patterns from regions showing between-group differences. O-LOAD individuals scored worse in neurocognitive measures of memory and overall functioning (pFDR<0.05). In imaging analyses, we observed that O-LOAD individuals showed decreased global connectivity in a cluster encompassing the left LC (peak = −4, −34, −32, pTFCE