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

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

METHODS:
We analyzed non-rapid eye movement sleep EEG 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, NfL, 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.