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

Korey Kam, Ankit Parekh, Ram A. Sharma, Andreia Andrade, Monica Lewin, Bresne Castillo, Omonigho M. Bubu, Nicholas J. Chua, Margo D. Miller, Anna E. Mullins, Lidia Glodzik, Lisa Mosconi, Nadia Gosselin, Kulkarni Prathamesh, Zhe Chen, Kaj Blennow, Henrik Zetterberg, Nisha Bagchi, Bianca Cavedoni, David M. RapoportIndu Ayappa, Mony J. De Leon, Eva Petkova, Andrew W. Varga, Ricardo S. Osorio

Research output: Contribution to journalArticlepeer-review

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Abstract

Background: Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ 42 , 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 Aβ 42 , 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 Aβ 42 , 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.

Original languageEnglish
Article number10
JournalMolecular Neurodegeneration
Volume14
Issue number1
DOIs
StatePublished - 21 Feb 2019

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