The interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals

Osorio, Ricardo S.; Ayappa, Indu; Mantua, Janna; Gumb, Tyler; Varga, Andrew W.; Mooney, Anne M.; Burschtin, Omar; Taxin, Zachary; During, Emmanuel; Spector, Nicole; Biagioni, Milton; Pirraglia, Elizabeth; Lau, Hiuyan; Zetterberg, Henrik; Blennow, Kaj; Lu, Shou En; Mosconi, Lisa; Glodzik, Lidia; Rapoport, David M.; Leon, Mony J. de

doi:10.1016/j.neurobiolaging.2013.12.030

Cited by 110 publications

(100 citation statements)

References 35 publications

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“…OSA is also associated with altered levels of AD biomarkers in CSF, including decreased levels of Aβ 42 and elevated levels of phosphorylated tau 123 . OSA and chronic obstructive pulmonary disease could contribute to AD processes via hypoxia, inflammation, or sleep disruption 124 .…”

Section: Respiratory and Sleep Disordersmentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

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The global burden of Alzheimer disease (AD), already the most common type of dementia, is expected to increase still further owing to population ageing. AD not only causes severe distress for patients and caregivers, but also results in a large economic burden on society. Current major challenges in AD include the lack of reliable biomarkers for its early diagnosis, as well as the lack of effective preventive strategies and treatments 1,2 . Thus, increased understanding of the molecular patho genesis of AD could lead to the development of improved diagnostic and therapeutic strategies.AD is conventionally regarded as a CNS disorder. However, increasing experimental, epidemiological and clinical evidence has suggested that manifestations of AD extend beyond the brain. These systemic alterations might not be simply secondary effects of the cerebral degeneration seen in AD, but could reflect under lying processes linked to progression of the disease. AD pathogenesis is complex, involving abnormal amyloid-β (Aβ) metabolism, tau hyperphosphorylation, oxidative stress, reactive glial and microglial changes, and other pathological events. Given that Aβ is a major hallmark of AD and a fertile area of research in this disease, this Review focuses on the systemic role of Aβ in AD. We discuss the communication between peripheral and central pools of Aβ, and describe interactions between systemic abnormalities and AD pathogenesis in the brain. We review emerging findings of associations between systemic abnormalities and Aβ metabolism, and describe how these associations might interact with or reflect on the central pathways of Aβ production and clearance. On the basis of these findings, we suggest that interactions between the brain and the periphery might have a crucial role in the development and progression of AD. Aβ biogenesis and catabolismA steady accrual of data from laboratories and clinics is providing increasing support for the concept that an imbalance between the production and clearance of Aβ is a very early (and often initiating) factor in AD 3 . Normal metabolism of Aβ and maintenance of the homeostatic balance between Aβ production and clearance is, therefore, essential to maintain brain health. In fact, physiological metabolism of Aβ occurs not only in the brain but also in the periphery, and communication between these regions is possible (FIG. 1). Central and peripheral production of AβAβ is derived from the proteolytic cleavage of amyloid precursor protein (APP), which is expressed not only in brain cells, including neurons, astrocytes and microglia, but also in peripheral organs and tissues, such as the Abstract | Alzheimer disease (AD) is the most common type of dementia, and is currently incurable; existing treatments for AD produce only a modest amelioration of symptoms. Research into this disease has conventionally focused on the CNS. However, several peripheral and systemic abnormalities are now understood to be linked to AD, and our understanding of how these alterations contribute to AD is becom...

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Section: Respiratory and Sleep Disordersmentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

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“…We hypothesized that conserved SWS would be associated with low CSF Aβ42 levels, while disrupted SWS would be associated with high Aβ42 levels. Given that reduced CSF Aβ42 levels or SWS duration can be associated with advanced age, 8 the apolipoprotein E-4 (ApoE4) allele, 8 sex, 9 lower education, 10 and sleep disordered breathing (SDB), 11 we also tested the extent to which the variation in CSF Aβ42 predicted by SWS were influenced by these factors.…”

Section: Significancementioning

confidence: 99%

“…Subjects were recruited from multiple community sources in NYC as previously described, 11 individuals with conditions that could affect brain structure or function were excluded.…”

Section: Study Design and Participantsmentioning

confidence: 99%

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

Varga

Wohlleber

Giménez

et al. 2016

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130

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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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“…Additionally, communitydwelling women affected by OSA were shown to present a higher risk of developing MCI or dementia [82]. It has also been demonstrated that OSA is associated with enhanced CSF levels of Aβ42 and phosphorylated tau in older adults presenting with the APOε3/3 alleles [83].…”

Section: Hypoxia Induced By Sleep Disordered Breathing (Sdb) Emamianmentioning

confidence: 99%

Is Sleep Disruption a Risk Factor for Alzheimer’s Disease?

Macedo

Balouch

Tabet

2017

JAD

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Sleep disturbances are routinely encountered in Alzheimer's disease (AD) and affect about 25-40% of patients in the mild-to-moderate stages of the disease. In many, sleep pathology may represent a symptom of the underlying neurodegeneration. However, a history of sleep disruption occurring years prior to onset of cognitive symptoms could represent a potential risk factor for AD. The aim of the present narrative review was to evaluate current evidence linking sleep disturbances with AD development and to understand the mechanisms that may contribute to this.Although the mechanisms by which poor sleep may contribute to AD genesis is not fully understood, emerging evidence linking disturbances in the sleep wake cycle with Aβ deposition is shedding light on the relationship between sleep pathology and the subsequent development of AD. Aβ burden appears to be enhanced by sleep-wake cycle disruptions and is suspected as being an important mechanism by which sleep disruptions contribute in AD development. Other mechanisms triggered by sleep disruption may also be involved in AD development, such as brain hypoxia, oxidative stress, circadian activity rhythms disturbances, overexpression of orexins and blood brain barrier impairment. Further understanding of the link between sleep disturbances and future development of AD is still needed before sleep disturbances are clearly marked as a preventable risk factor for AD. In these circumstances, early lifestyle interventions to help increase the quantity and quality of sleep may have a favorable outcome on decreasing the incidence of AD and this needs to be investigated further.

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The interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals

Cited by 110 publications

References 35 publications

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

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

Is Sleep Disruption a Risk Factor for Alzheimer’s Disease?

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