Are infraslow oscillations the missing link between sleep and Alzheimer's?

INTRODUCTION

Locus coeruleus (LC) and glymphatic dysfunction have been linked both to Alzheimer's disease (AD) and, recently, to infraslow oscillation (ISO) in sleep spindle (sigma) activity (ISO). Here we hypothesize ISO integrity is a critical link between sleep and AD.

METHODS

We analyzed non-rapid eye movement sleep electroencephalogram (EEG) data from AD participants and controls, extracting ISO peak amplitude, intrinsic frequency, and bandwidth from the sigma-power time-course. We assessed group differences and correlations with plasma biomarkers (Aβ42/40, pTau181, pTau217, neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP]).

RESULTS

ISO peak amplitude was significantly reduced in AD, while intrinsic frequency and bandwidth were preserved. ISO peak amplitude showed a trend-level association with Aβ42/40, whereas ISO bandwidth was positively associated with NfL, and showed trends with GFAP and lower verbal memory retention.

DISCUSSION: Selective weakening of ISO in AD is consistent with LC dysfunction and impaired glymphatic cycling. ISO may be a novel mechanism and electrophysiological marker linking sleep microarchitecture to AD pathology.