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- Mander, B. A., et al.
(författare)
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Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to beta-amyloid positivity
- 2022
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 45:9
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives Fast frequency sleep spindles are reduced in aging and Alzheimer's disease (AD), but the mechanisms and functional relevance of these deficits remain unclear. The study objective was to identify AD biomarkers associated with fast sleep spindle deficits in cognitively unimpaired older adults at risk for AD. Methods Fifty-eight cognitively unimpaired, beta-amyloid-negative, older adults (mean +/- SD; 61.4 +/- 6.3 years, 38 female) enriched with parental history of AD (77.6%) and apolipoprotein E (APOE) epsilon 4 positivity (25.9%) completed the study. Cerebrospinal fluid (CSF) biomarkers of central nervous system inflammation, beta-amyloid and tau proteins, and neurodegeneration were combined with polysomnography (PSG) using high-density electroencephalography and assessment of overnight memory retention. Parallelized serial mediation models were used to assess indirect effects of age on fast frequency (13 to <16Hz) sleep spindle measures through these AD biomarkers. Results Glial activation was associated with prefrontal fast frequency sleep spindle expression deficits. While adjusting for sex, APOE epsilon 4 genotype, apnea-hypopnea index, and time between CSF sampling and sleep study, serial mediation models detected indirect effects of age on fast sleep spindle expression through microglial activation markers and then tau phosphorylation and synaptic degeneration markers. Sleep spindle expression at these electrodes was also associated with overnight memory retention in multiple regression models adjusting for covariates. Conclusions These findings point toward microglia dysfunction as associated with tau phosphorylation, synaptic loss, sleep spindle deficits, and memory impairment even prior to beta-amyloid positivity, thus offering a promising candidate therapeutic target to arrest cognitive decline associated with aging and AD.
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| 2. |
- Olsson, Martin, 1978, et al.
(författare)
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Sleep Deprivation and CSF Biomarkers for Alzheimer Disease.
- 2018
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Ingår i: Sleep. - : Oxford University Press (OUP). - 1550-9109 .- 0161-8105. ; 41:5
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the cumulative effect of 5 consecutive nights of partial sleep deprivation on a panel of cerebrospinal fluid (CSF) biomarkers in healthy adults.A randomized, cross-over study conducted at the University of Gothenburg. The participants (N=13) were healthy adults (20-40 years of age) with a normal sleeping pattern. The participants underwent a baseline sleep period consisting of 5 nights with 8h spent in bed. A subsequent period with partial sleep deprivation (PSD) consisted of 5 nights of maximum 4h of sleep per night. Four participants were also subjected to a prolonged period of PSD consisting of 8 nights with 4h of sleep per night. Sleep was monitored by means of observation, actigraphy and continuous polysomnographic recordings. CSF samples were collected by routine lumbar puncture after each period. CSF biomarkers included the 38, 40 and 42 amino acid-long Aβ isoforms, total-tau, phospho-tau, orexin, monoamine metabolites (MHPG, HVA and 5-HIAA), neuron-derived biomarkers (NF-L, NSE, FABP) and astro- and microglia-derived biomarkers (GFAP, S-100B, YKL-40).PSD was associated with a 27% increase in CSF orexin concentrations (P= 0.001). No PSD-related changes in CSF biomarkers for amyloid build-up in the brain, Alzheimer disease (AD)-type neurodegeneration or astroglial activation were observed. PSD led to a shortening of time spent in all sleep stages except slow wave sleep (SWS).5-8 consecutive nights of PSD, with preserved SWS, increased CSF orexin but had no effect on CSF biomarkers for amyloid deposition, neuronal injury and astroglial activation.
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| 3. |
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| 4. |
- Targa, A., et al.
(författare)
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Decrease in sleep depth is associated with higher cerebrospinal fluid neurofilament light levels in patients with Alzheimer's disease
- 2021
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 44:2
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Tidskriftsartikel (refereegranskat)abstract
- Study objectives: The majority of studies investigating the association between sleep and Alzheimer's disease (AD) biomarkers have been performed in healthy participants. Our objective was to investigate the association between sleep and several biomarkers that reflect distinct aspects of AD physiopathology. Methods: The cohort included 104 individuals with mild-moderate AD. The participants were submitted to one-night polysomnography, and cerebrospinal fluid was collected in the following morning to measure the selected biomarkers associated with amyloid deposition, tau pathology, neurodegeneration, axonal damage, synaptic integrity, neuroinflammation, and oxidative damage. Results: There was a positive correlation between neurofilament light (NF-L) and the time spent in stage 1 of non-rapid eyes movement (NREM) (N1) sleep and a negative correlation between this marker and the time spent in stage 3 of NREM (N3) sleep. Accordingly, we observed that deep sleep was associated with lower levels of NF-L, whereas light sleep increased the probability of having higher levels of this marker. Furthermore, chitinase-3-like-1 (YKL-40) was negatively correlated with sleep efficiency, the time spent in stage 2 of NREM (N2) sleep, and the time spent in N3 sleep. Conversely, there was a positive correlation between N3 sleep and the oxidative protein damage markers N-epsilon-(carboxyethyl)lysine and N-epsilon-(malondialdehyde)lysine. Conclusions: There were significant correlations between sleep parameters and AD biomarkers related to axonal damage and neuroinflammation, such as NF-L and YKL-40. A lack of deep sleep was associated with higher levels of NF-L. This highlights a potential role for NF-L as a biomarker of sleep disruption in patients with mild-moderate AD in addition to its role in predicting neurodegeneration and cognitive decline.
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| 5. |
- Varga, A. W., et al.
(författare)
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Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid A beta 42 Levels in Cognitively Normal Elderly
- 2016
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 39:11, s. 2041-2048
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: Emerging evidence suggests a role for sleep in contributing to the progression of Alzheimer disease (AD). Slow wave sleep (SWS) is the stage during which synaptic activity is minimal and clearance of neuronal metabolites is high, making it an ideal state to regulate levels of amyloid beta (A beta). We thus aimed to examine relationships between concentrations of A beta 42 in the cerebrospinal fluid (CSF) and measures of SWS in cognitively normal elderly subjects. Methods: Thirty-six subjects underwent a clinical and cognitive assessment, a structural MRI, a morning to early afternoon lumbar puncture, and nocturnal polysomnography. Correlations and linear regression analyses were used to assess for associations between CSF A beta 42 levels and measures of SWS controlling for potential confounders. Resulting models were compared to each other using ordinary least squared linear regression analysis. Additionally, the participant sample was dichotomized into "high" and "low" A beta 42 groups to compare SWS bout length using survival analyses. Results: A significant inverse correlation was found between CSF A beta 42 levels, SWS duration and other SWS characteristics. Collectively, total SWA in the frontal lead was the best predictor of reduced CSF A beta 42 levels when controlling for age and ApoE status. Total sleep time, time spent in NREM1, NREM2, or REM sleep were not correlated with CSF A beta 42. Conclusions: In cognitively normal elderly, reduced and fragmented SWS is associated with increases in CSF A beta 42, suggesting that disturbed sleep might drive an increase in soluble brain A beta levels prior to amyloid deposition.
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