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Mol Neurodegener. 2019 Feb 21;14(1):10. doi: 10.1186/s13024-019-0309-5.

Sleep oscillation-specific associations with Alzheimer's disease CSF biomarkers: novel roles for sleep spindles and tau.

Author information

1
Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1232, New York, NY, 10029, USA.
2
Department of Psychiatry, NYU School of Medicine, New York, NY, 10016, USA.
3
Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, 10962, USA.
4
Department of Neurology, Weill Cornell Medical College, New York, NY, USA.
5
Center for Advanced Research in Sleep Medicine (CARSM), Department of Psychology, Hospital du Sacré-Coeur de Montreal, Montreal, Quebec, Canada and Université de Montreal, Montreal, Quebec, Canada.
6
Institute of Neuroscience and Psychiatry, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
7
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
8
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
9
UK Dementia Research Institute at UCL, London, UK.
10
Child and Adolescent Psychiatry, NYU School of Medicine, New York, NY, 10016, USA.
11
Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1232, New York, NY, 10029, USA. andrew.varga@mssm.edu.
12
Department of Psychiatry, NYU School of Medicine, New York, NY, 10016, USA. ricardo.osoriosuarez@nyulangone.org.
13
Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, 10962, USA. ricardo.osoriosuarez@nyulangone.org.

Abstract

BACKGROUND:

Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ42, P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals.

METHODS:

One-night in-lab nocturnal polysomnography (NPSG) and morning to early afternoon CSF collection were performed to measure CSF Aβ42, P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time.

RESULTS:

Spindle density during NREM stage 2 (N2) sleep was negatively correlated with CSF Aβ42, P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD.

CONCLUSIONS:

Reduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline.

PMID:
30791922
PMCID:
PMC6385427
DOI:
10.1186/s13024-019-0309-5
[Indexed for MEDLINE]
Free PMC Article

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