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

Abstract INTRODUCTION Locus coeruleus and glymphatic dysfunction are 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 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 and 217, NfL, GFAP). RESULTS ISO peak amplitude was significantly reduced in AD, while intrinsic frequency and bandwidth were preserved. ISO peak amplitude positively correlated with Aβ42/40 ratio, and ISO bandwidth correlated with GFAP and NfL levels, and with lower verbal memory retention. DISCUSSION Such 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.