Obstructive sleep apnea decreases central nervous system–derived proteins in the cerebrospinal fluid

Ju, Yo‐El; Finn, Mary Beth; Sutphen, Courtney L.; Herries, Elizabeth M.; Jerome, Gina M.; Ladenson, Jack H.; Crimmins, Daniel L.; Fagan, Anne M.; Holtzman, David M.

doi:10.1002/ana.24672

Cited by 131 publications

(141 citation statements)

References 23 publications

(38 reference statements)

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“…Significant inverse associations between SWS and CSF Aβ40 have been found previously in a cohort containing younger middle aged (53.2 ± 5.7) individuals. 25 In any case, the consistent inverse associations between SWS and Aβ42 remain of special interest as this peptide appears to have the greatest propensity to deposit into insoluble plaques.…”

Section: Discussionmentioning

confidence: 99%

Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Aβ42 Levels in Cognitively Normal Elderly

Varga

Wohlleber

Giménez

et al. 2016

Sleep

153

140

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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 (Aβ). We thus aimed to examine relationships between concentrations of Aβ42 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 Aβ42 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" Aβ42 groups to compare SWS bout length using survival analyses. Results: A significant inverse correlation was found between CSF Aβ42 levels, SWS duration and other SWS characteristics. Collectively, total SWA in the frontal lead was the best predictor of reduced CSF Aβ42 levels when controlling for age and ApoE status. Total sleep time, time spent in NREM1, NREM2, or REM sleep were not correlated with CSF Aβ42. Conclusions: In cognitively normal elderly, reduced and fragmented SWS is associated with increases in CSF Aβ42, suggesting that disturbed sleep might drive an increase in soluble brain Aβ levels prior to amyloid deposition.

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Section: Discussionmentioning

confidence: 99%

Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Aβ42 Levels in Cognitively Normal Elderly

Varga

Wohlleber

Giménez

et al. 2016

Sleep

153

140

View full text Add to dashboard Cite

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“…Sleep apnea is one of the most common causes of blood pressure non-dipping. Further, OSA is associated with a reduction of slow wave sleep and lower A␤ 40 in CSF, but in normal control there is an inverse correlation between CSF amyloid level and slow wave activity [36]. Brain interstitial fluid washed through glymphatic system is absorbed into dural lymphatic system and subsequently drained to cervical lymph node [37].…”

Section: Discussionmentioning

confidence: 99%

“…Brain interstitial fluid washed through glymphatic system is absorbed into dural lymphatic system and subsequently drained to cervical lymph node [37]. Repetitive apnea-related intracranial pressure swings are suggested to impair upstream interstitial fluid clearance via glymphatic system [36]. Therefore, reduced amyloid clearance along with increased amyloid production in OSA could accentuate amyloid deposition.…”

Section: Discussionmentioning

confidence: 99%

Amyloid Burden in Obstructive Sleep Apnea

Yun

Lee

et al. 2017

JAD

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Abstract. To test the hypothesis that excessive amyloid deposition is a biological link between obstructive sleep apnea (OSA) and Alzheimer's disease, we determined whether OSA increases cerebral amyloid burden, relative to controls, using Pittsburgh Compound B (PiB) PET imaging. The subjects were adult participants (age 50-65 years) from the Korean Genome and Epidemiology Study. Polysomnography, brain MRI including 3D images, and a detailed neuro-cognitive function test battery were done in 2011-2012. Nineteen OSA subjects (Apnea-Hypopnea Index [AHI] ≥15/h, 21.2 ± 5.1/h; age 58.5 ± 4.1 years; 9 male) and 19 controls (AHI 1.8 ± 1.3/h; age 58.5 ± 4.2 years; 9 male) underwent 60-min dynamic 11 C-PiB PET. All subjects were right-handed with normal cognitive function and brain MRI. Controls were matched by age, gender, education, and APOE genotype. A voxel-wise comparison of PiB-PET images between the two groups was performed after spatial and count normalization with cerebellar gray matter as a reference. Covariates included the status of sleep duration, hypertension, diabetes, body mass index, exercise, depressive mood, smoking, and alcohol drinking. Cortical thickness on 3D MRI was also measured and compared between the two groups. The OSA group showed a higher PiB deposition in the right posterior cingulate gyrus and right temporal cortex (corrected p < 0.05). There was no area of higher uptake in the control compared with OSA. Regional differences in cortical thickness were not significant. The study suggests that OSA accelerates amyloid deposition and may contribute to the development or progression of Alzheimer's disease.

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“…To our knowledge, these have never been fully clinically tested in the context of SVD. A recent study demonstrated that obstructive sleep apnea (OSA) causes a reduction in the concentration of brain-derived proteins in CSF after slow wave sleep(123). The authors suggest that OSA causes alterations in CSF-ISF exchange causing these proteins to become trapped when they would normally be cleared out into the CSF.…”

Section: Targeting Glymphatics For Treatment and Prevention Of Svdmentioning

confidence: 99%

Perivascular spaces, glymphatic dysfunction, and small vessel disease

2017

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Cerebral small vessel diseases (SVD) range broadly in etiology but share a remarkably overlapping pathology. Features of SVD including enlarged perivascular spaces and formation of abluminal protein deposits cannot be completely explained by the putative pathophysiology. The recently discovered glymphatic system provides a new perspective to potentially address these gaps. This work provides a comprehensive review of the known factors that regulate glymphatic function and the disease mechanisms underlying glymphatic impairment emphasizing the role that aquaporin-4 (AQP4)-lined perivascular spaces, cerebrovascular pulsatility, and metabolite clearance play in normal CNS physiology. This review also discusses the implications that glymphatic impairment may have on SVD inception and progression with the aim of exploring novel therapeutic targets and highlighting the key questions that remain to be answered.

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Obstructive sleep apnea decreases central nervous system–derived proteins in the cerebrospinal fluid

Cited by 131 publications

References 23 publications

Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Aβ42 Levels in Cognitively Normal Elderly

Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Aβ42 Levels in Cognitively Normal Elderly

Amyloid Burden in Obstructive Sleep Apnea

Perivascular spaces, glymphatic dysfunction, and small vessel disease

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