Since uninterrupted sleep is a prerequisite for efficient glymphatic clearance, it is not surprising that glymphatic flow is suppressed in AD.78 Glymphatic clearance is also suppressed in APP/PS1 mice at the age of 6 months, when amyloid starts to deposit.34 This observation has been extended to clinical PET imaging of CSF flow, describing reduced brain tissue clearance in AD patients with mild cognitive impairment.33 Nevertheless, it remains unclear if sleep disturbances precede glymphatic dysfunction. This evidence concerns the gene PSEN1 and Alzheimer disease.