Amyloid beta-independent sleep markers associated with early regional tau burden and cortical thinning.

IF 4 Q1 CLINICAL NEUROLOGY Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2024-07-29 eCollection Date: 2024-07-01 DOI:10.1002/dad2.12616

Laura Stankeviciute, Jasmeer P Chhatwal, Raina Levin, Valentina Pinilla, Aaron P Schultz, Susan Redline, Keith A Johnson, Reisa A Sperling, Nataliia Kozhemiako, Shaun Purcell, Ina Djonlagic

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Abstract

Introduction: Sleep is crucial for memory consolidation and the clearance of toxic proteins associated with Alzheimer's disease (AD). We examined the association between sleep characteristics and imaging biomarkers of early amyloid beta (Aβ) and tau pathology as well as neurodegeneration in brain regions known to be affected in the incipient stages of AD.

Methods: Thirty-nine cognitively unimpaired (CU) participants of the Harvard Aging Brain Study underwent at-home polysomnography as well as tau positron emission tomography (flortaucipir-PET), amyloid PET (Pittsburgh compound B [PiB]-PET), and magnetic resonance imaging-derived assessment of cortical thickness (CT).

Results: Increased N1 sleep was associated with a higher tau PET signal (β = 0.009, p = 0.001) and lower CT in the temporal composite region of interest (β = -0.017, p = 0.007). Decreased slow-wave sleep (SWS) was associated with higher tau burden in the temporal composite (β = -0.008, p = 0.005) and lower CT (β = 0.008, p = 0.002), even after controlling for global PiB-PET.

Discussion: In CU older adults, lower SWS and higher N1 sleep were associated with higher tau burden and lower CT in brain regions associated with early tau deposition and vulnerable to AD-related neurodegeneration through mechanisms dissociable from amyloid deposition.

Highlights: We report the results of an observational study, which leveraged -a well-characterized cohort of healthy aging (Harvard Aging Brain Study) by adding in-home full polysomnograms.By adding at-home polysomnograms to this unique and deeply phenotyped cohort, we examined variations in sleep architecture that are associated with Alzheimer's disease (AD) pathologic changes.Our results confirmed the association of sleep changes with early tau and cortical neurodegenerative changes that were independent of amyloid.The results will be of importance in monitoring sleep-related variations in relation to the natural history of AD pathology and in designing sleep-focused clinical trials.

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与淀粉样β无关的睡眠标记物与早期区域性 tau 负荷和皮质变薄有关。

简介睡眠对记忆巩固和清除与阿尔茨海默病（AD）相关的有毒蛋白质至关重要。我们研究了睡眠特征与早期淀粉样蛋白β（Aβ）和tau病理成像生物标志物以及已知在阿尔茨海默病萌芽阶段受影响的脑区神经退行性变之间的关系：哈佛大学脑老化研究的39名认知功能未受损（CU）的参与者接受了居家多导睡眠监测以及tau正电子发射断层扫描（floraucipir-PET）、淀粉样蛋白PET（匹兹堡化合物B [PiB]-PET）和磁共振成像衍生的皮质厚度评估（CT）：N1睡眠增加与较高的tau PET信号（β = 0.009，p = 0.001）和较低的颞叶复合相关区域CT（β = -0.017，p = 0.007）有关。慢波睡眠（SWS）的减少与颞叶综合区域较高的 tau 负荷（β = -0.008，p = 0.005）和较低的 CT（β = 0.008，p = 0.002）相关，即使在控制了全局 PiB-PET 后也是如此：讨论：在中老年人中，较低的SWS和较高的N1睡眠与较高的tau负荷和较低的CT有关，这些脑区与早期tau沉积有关，并且容易通过与淀粉样蛋白沉积不同的机制发生与AD相关的神经变性：我们报告了一项观察性研究的结果，该研究利用了一个特征明确的健康老龄化队列（哈佛大学脑老龄化研究），增加了家庭多导睡眠图。我们的研究结果证实了睡眠变化与早期tau和皮质神经退行性变化之间的关联，而这些变化与淀粉样蛋白无关。

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来源期刊

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Medicine-Psychiatry and Mental Health

CiteScore

7.80

自引率

7.50%

发文量

101

审稿时长

8 weeks

期刊介绍： Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.