title: Progressive age-related changes in sleep and EEG profiles in the PLB1Triple mouse model of Alzheimer's disease.
abstract: Sleep disturbances are common in Alzheimer's disease (AD) and now assumed to contribute to disease onset and progression. Here, we investigated whether activity, sleep/wake pattern, and electroencephalogram (EEG) profiles are altered in the knock-in PLB1Triple mouse model from 5 to 21 months of age. PLB1Triple mice displayed a progressive increase in wakefulness and non-rapid eye movement sleep fragmentation from 9 months onward, whereas PLB1WT wild type controls showed such deterioration only at 21 months. Impaired habituation to spatial novelty was also detected in PLB1Triple mice. Hippocampal power spectra of transgenic mice revealed progressive, vigilance stage-, brain region-, and age-specific changes. Age had an impact on EEG spectra in both cohorts but led to accelerated genotype-dependent differences, ultimately affecting all bands at 21 months. Overall, although PLB1Triple animals display only subtle amyloid and tau pathologies, robust sleep-wake and EEG abnormalities emerged. We hypothesize that such endophenotypes are sensitive, noninvasive, and reliable biomarker to identify onset and progression of AD.
authors.affiliation: Department of Biomedical Sciences, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
authors.forename: Amar
authors.initials: A
authors.lastname: Jyoti
authors.affiliation: Department of Biomedical Sciences, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Plano
authors.affiliation: Department of Biomedical Sciences, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
authors.forename: Gernot
authors.initials: G
authors.lastname: Riedel
authors.affiliation: Department of Biomedical Sciences, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK. Electronic address: b.platt@abdn.ac.uk.
authors.forename: Bettina
authors.initials: B
authors.lastname: Platt
mesh_terms: D000375:Aging / Q000502:physiology* / Q000523:psychology; D000544:Alzheimer Disease / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004569:Electroencephalography; D008822:Mice, Transgenic; D012890:Sleep; D012893:Sleep Wake Disorders / Q000150:complications / Q000503:physiopathology / Q000523:psychology
keywords: APP; Alzheimer’s disease; EEG; PS1; Sleep; Tau