Timely coupling of sleep spindles and slow waves is linked to early amyloid-β burden and predicts memory decline
- University of Liège, Belgium
- Physip, France
- Université de Montréal, Canada
Abstract
Sleep alteration is a hallmark of ageing and emerges as a risk factor for Alzheimer's disease (AD). While the fine-tuned coalescence of sleep microstructure elements may influence age-related cognitive trajectories, its association with AD processes is not fully established. Here, we investigated whether the coupling of spindles and slow waves is associated with early amyloid-beta (Aβ) brain burden, a hallmark of AD neuropathology, and cognitive change over 2 years in 100 healthy individuals in late-midlife (50-70y; 68 women). We found that, in contrast to other sleep metrics, earlier occurrence of spindles on slow-depolarisation slow waves is associated with higher medial prefrontal cortex Aβ burden (p=0.014, r²β*=0.06), and is predictive of greater longitudinal memory decline in a large subsample (p=0.032, r²β*=0.07, N=66). These findings unravel early links between sleep, AD-related processes and cognition and suggest that altered coupling of sleep microstructure elements, key to its mnesic function, contributes to poorer brain and cognitive trajectories in ageing.
Data availability
The data and analysis scripts supporting the results included in this manuscript are publicly available via the following open repository: https://gitlab.uliege.be/CyclotronResearchCentre/Public/fasst/slow-wave-spindle-coupling-and-amyloid. We used Matlab script for MRI and PET data processing and to detect slow waves and spindles as well as their coupling, while we used SAS for statistical analyses. The raw data could be identified and linked to a single subject and represent a huge amount of data (> 200 Gb). Researchers willing to access the raw data should send a request to the corresponding author (GV). Data sharing will require evaluation of the request by the Medicine Faculty-Hostpital Ethic Committee of the University of Liège, Belgium and the signature of a data transfer agreement (DTA).
Article and author information
Author details
Christophe Phillips
Funding
Fonds De La Recherche Scientifique - FNRS (FRSM 3.4516.11)
- Gilles Vandewalle
Fédération Wallonie-Bruxelles (ARC-SLEEPDEM 17/09)
- Daphne Chylinski
- Maxime Van Egroo
- Justinas Narbutas
- Christine Bastin
- Christophe Phillips
- Fabienne Collette
- Pierre Maquet
- Gilles Vandewalle
European Regional Development Fund (RAdiomed)
- Daphne Chylinski
- Maxime Van Egroo
- Justinas Narbutas
- Vincenzo Muto
- Mohamed Ali Bahri
- Eric Salmon
- Christine Bastin
- Christophe Phillips
- Fabienne Collette
- Pierre Maquet
- Gilles Vandewalle
Canadian Institutes of Health Research (grant number 190750)
- Julie Carrier
- Jean-Marc Lina
General Electric (ISS290)
- Eric Salmon
- Christine Bastin
- Christophe Phillips
- Fabienne Collette
- Pierre Maquet
- Gilles Vandewalle
Fonds De La Recherche Scientifique - FNRS
- Maxime Van Egroo
- Christine Bastin
- Christophe Phillips
- Fabienne Collette
- Gilles Vandewalle
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The study was registered with EudraCT 2016-001436-35. All procedures were approved by the Hospital-Faculty Ethics Committee of ULiège. All participants signed an informed consent prior to participating in the study.
Copyright
© 2022, Chylinski et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Timely coupling of sleep spindles and slow waves is linked to early amyloid-β burden and predicts memory decline
eLife 11:e78191.
https://doi.org/10.7554/eLife.78191
Further reading
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We present near-atomic-resolution cryoEM structures of the mammalian voltage-gated potassium channel Kv1.2 in open, C-type inactivated, toxin-blocked and sodium-bound states at 3.2 Å, 2.5 Å, 3.2 Å, and 2.9 Å. These structures, all obtained at nominally zero membrane potential in detergent micelles, reveal distinct ion-occupancy patterns in the selectivity filter. The first two structures are very similar to those reported in the related Shaker channel and the much-studied Kv1.2–2.1 chimeric channel. On the other hand, two new structures show unexpected patterns of ion occupancy. First, the toxin α-Dendrotoxin, like Charybdotoxin, is seen to attach to the negatively-charged channel outer mouth, and a lysine residue penetrates into the selectivity filter, with the terminal amine coordinated by carbonyls, partially disrupting the outermost ion-binding site. In the remainder of the filter two densities of bound ions are observed, rather than three as observed with other toxin-blocked Kv channels. Second, a structure of Kv1.2 in Na+ solution does not show collapse or destabilization of the selectivity filter, but instead shows an intact selectivity filter with ion density in each binding site. We also attempted to image the C-type inactivated Kv1.2 W366F channel in Na+ solution, but the protein conformation was seen to be highly variable and only a low-resolution structure could be obtained. These findings present new insights into the stability of the selectivity filter and the mechanism of toxin block of this intensively studied, voltage-gated potassium channel.
