Alterations of sleep oscillations in Alzheimer's disease: A potential role for GABAergic neurons in the cortex, hippocampus, and thalamus

Abstract

Sleep abnormalities are widely reported in patients with Alzheimer’s disease (AD) and are linked to cognitive impairments. Sleep abnormalities could be potential biomarkers to detect AD since they are often observed at the preclinical stage. Moreover, sleep could be a target for early intervention to prevent or slow AD progression. Thus, here we review changes in brain oscillations observed during sleep, their connection to AD pathophysiology and the role of specific brain circuits. Slow oscillations (0.1–1 Hz), sleep spindles (8–15 Hz) and their coupling during non-REM sleep are consistently reduced in studies of patients and in AD mouse models although the timing and magnitude of these alterations depends on the pathophysiological changes and the animal model studied. Changes in delta (1–4 Hz) activity are more variable. Animal studies suggest that hippocampal sharp-wave ripples (100–250 Hz) are also affected. Reductions in REM sleep amount and slower oscillations during REM are seen in patients but less consistently in animal models. Thus, changes in a variety of sleep oscillations could impact sleep-dependent memory consolidation or restorative functions of sleep. Recent mechanistic studies suggest that alterations in the activity of GABAergic neurons in the cortex, hippocampus and thalamic reticular nucleus mediate sleep oscillatory changes in AD and represent a potential target for intervention. Longitudinal studies of the timing of AD-related sleep abnormalities with respect to pathology and dysfunction of specific neural networks are needed to identify translationally relevant biomarkers and guide early intervention strategies to prevent or delay AD progression.

Keywords

• Beta-amyloid
• Tau
• Sleep spindle
• Slow wave
• Sharp-wave ripple
• EEG