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Holth JK, Mahan TE, Robinson GO, et al. Altered sleep and EEG power in the P301S Tau transgenic mouse model. Ann Clin Transl Neurol. 2017;4(3):180-190doi: 10.1002/acn3.390.
Holth, J. K., Mahan, T. E., Robinson, G. O., Rocha, A., & Holtzman, D. M. (2017). Altered sleep and EEG power in the P301S Tau transgenic mouse model. Annals of clinical and translational neurology, 4(3), 180-190. https://doi.org/10.1002/acn3.390
Holth, Jerrah K, et al. "Altered sleep and EEG power in the P301S Tau transgenic mouse model." Annals of clinical and translational neurology vol. 4,3 (2017): 180-190. doi: https://doi.org/10.1002/acn3.390
Holth JK, Mahan TE, Robinson GO, Rocha A, Holtzman DM. Altered sleep and EEG power in the P301S Tau transgenic mouse model. Ann Clin Transl Neurol. 2017 Feb 15;4(3):180-190. doi: 10.1002/acn3.390. eCollection 2017 Mar. PMID: 28275652; PMCID: PMC5338139.
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Ann Clin Transl Neurol. 2017 Feb 15;4(3):180-190. doi: 10.1002/acn3.390. eCollection 2017 Mar.

Altered sleep and EEG power in the P301S Tau transgenic mouse model.

Annals of clinical and translational neurology

Jerrah K Holth, Thomas E Mahan, Grace O Robinson, Andreia Rocha, David M Holtzman

Affiliations

  1. Department of Neurology Hope Center for Neurological Disorders, and the Knight Alzheimer's Disease Research Center Washington University School of Medicine St. Louis Missouri 63110.

PMID: 28275652 PMCID: PMC5338139 DOI: 10.1002/acn3.390

Abstract

OBJECTIVE: Sleep disturbances are prevalent in human tauopathies yet despite the importance of sleep, little is known about its relationship with tau pathology. Here, we investigate this interaction by analyzing sleep and tau pathology throughout tauopathy disease progression in P301S human tau transgenic mice.

METHODS: P301S and wild-type mice were analyzed by electroencephalography (EEG)/electromyography at 3, 6, 9, and 11 months of age for sleep/wake time, EEG power, and homeostatic response. Cortical volume and tau pathology was also assessed by anti-phospho-tau AT8 staining.

RESULTS: P301S tau mice had significantly decreased rapid eye movement (REM) sleep at 9 months of age and decreased REM and non-REM (NREM) sleep as well as increased wakefulness at 11 months. Sleep loss was characterized by fewer wake, REM, and NREM bouts, increased wake bout duration, and decreased sleep bout duration. Decreased REM and NREM sleep was associated with increased brainstem tau pathology in the sublaterodorsal area and parafacial zone, respectively. P301S mice also showed increased EEG power at 6 and 9 months of age and decreased power at 11 months. Decreased EEG power was associated with decreased cortical volume. Despite sleep disturbances, P301S mice maintained homeostatic response to sleep deprivation.

INTERPRETATION: Our results indicate that tau pathology is associated with sleep disturbances that worsen with age and these changes may be related to tau pathology in brainstem sleep regulating regions as well as neurodegeneration. Tau-induced sleep changes could affect disease progression and be a marker for therapeutic efficacy in this and other tauopathy models.

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