Evidence suggests that amyloid-beta (Abeta) deposition accompanies sleep deficits in Alzheimer’s disease (AD). However, it remains unknown whether impaired sleep and changes in plasma Abeta levels run in parallel in amnestic mild cognitive impairment (aMCI) subjects, and whether both markers are further associated with cortical thinning in canonical AD regions. To address these issues, we first evaluated whether plasma Abeta levels are related to changes in sleep physiology and/or cortical thinning in aMCI subjects. Second, we investigated if sleep deficits and/or increased Abeta levels accounted for cortical thinning in aMCI subjects. Overnight polysomnographic (PSG) recordings, cerebral magnetic resonance imaging (MRI), and plasma Abeta levels were obtained from 21 aMCI patients and 21 healthy older (HO) subjects. A sleep technician performed scoring of sleep stages, and cortical thickness was measured by using the analysis pipeline of Freesurfer. aMCI, but not HO subjects, showed significant relationships between disrupted slow-wave sleep (SWS) and increased plasma levels of Abeta42. We also found that shortened rapid-eye movement (REM) sleep in aMCI correlated with thinning of the posterior cingulate, precuneus, and postcentral gyrus; whereas higher levels of Abeta40 and Abeta42 accounted for grey matter (GM) loss of posterior cingulate and entorhinal cortex, respectively. These results support the relationship between Abeta and altered sleep physiology previously observed in animal models of AD amyloidosis, and provide precise cortical correlates of these changes in older adults with aMCI.