Dataset Information

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

ABSTRACT:

Background

Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF A?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 A?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 A?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.

SUBMITTER: Kam K

PROVIDER: S-EPMC6385427 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Kam Korey K Parekh Ankit A Sharma Ram A RA Andrade Andreia A Lewin Monica M Castillo Bresne B Bubu Omonigho M OM Chua Nicholas J NJ Miller Margo D MD Mullins Anna E AE Glodzik Lidia L Mosconi Lisa L Gosselin Nadia N Prathamesh Kulkarni K Chen Zhe Z Blennow Kaj K Zetterberg Henrik H Bagchi Nisha N Cavedoni Bianca B Rapoport David M DM Ayappa Indu I de Leon Mony J MJ Petkova Eva E Varga Andrew W AW Osorio Ricardo S RS

Molecular neurodegeneration 20190221 1

<h4>Background</h4>Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ<sub>42</sub>, P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals.<h4>Methods</h4>One-night in-lab nocturnal polysomnography (NPSG) and morning to early afternoon CSF collection were performed to measure CSF Aβ<sub>42</su ...[more]

PMID: 30791922

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Project description:BackgroundDelirium and dementia share symptoms of cognitive dysfunctions, and mechanisms of neuroinflammation appear involved in both conditions. Triggering receptor expressed on myeloid cells 2 (TREM2) is linked to dementia and neurodegenerative disease. It encodes expression of an innate immune receptor in the brain expressed by microglia. The level of the soluble fragment of TREM2 (sTREM2) is reported to increase in the cerebrospinal fluid (CSF) already in prodromal and asymptomatic Alzheimer's disease.MethodsWe analyzed the level of CSF sTREM2 in relation to delirium and dementia. The study included patients with or without pre-existing dementia who underwent acute hip fracture surgery (n = 120), and some of the patients developed delirium (n = 65). A medical delirium cohort (n = 26) was also examined. ELISA was used to determine the level of sTREM2 in CSF.ResultsDelirium was associated with a higher level of CSF sTREM2 only among those without pre-existing dementia (p = 0.046, n = 15, n = 44), particularly among patients developing delirium after CSF sampling (p = 0.02, n = 7, n = 44). Between patients with dementia, there was no group difference, but the CSF sTREM2 level increased with waiting time for surgery (rS = 0.39, p = 0.002, n = 60) and correlated well with the CSF Alzheimer's disease biomarkers, Aβ42, and t-tau/p-tau (rS = 0.40, p = 0.002, rS = 0.46, p < 0.001/ rS = 0.49, p < 0.001, n = 60). Among patients with dementia, the level of Aβ38 and Aβ40 also correlated positively with sTREM2 in CSF (Aβ38MSDrS = 0.44, p = 0.001; Aβ40MSDrS = 0.48, p < 0.001; Aβ42MSDrS = 0.43, p < 0.001, n = 60).ConclusionThe findings reinforce the involvement of neuroinflammation in delirium, yet with separate responses in patients with or without pre-existing dementia. Our findings support the concept of primed microglia in neurodegenerative disease and central immune activation after a peripheral trauma in such patients. A CSF biomarker panel of neuroinflammation might be valuable to prevent delirium by identifying patients at risk.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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