Grollero, D.; Gabb, V.; Blackman, J.; de Vivo, L.; Coulthard, E.; Bellesi, M.

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 (A{beta}42/40, 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 A{beta}42/40 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.