Short sleep duration is associated with lower cerebrospinal fluid amyloid beta 42 levels in midlife: a preliminary report.
Short sleep duration is associated with lower cerebrospinal fluid amyloid beta 42 levels in midlife: a preliminary report.
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睡眠时间短与中年时期脑脊液淀粉样蛋白 42 水平较低有关：初步报告。
作者：
Gibson,Madeline;Nicolazzo,Jessica;Cavuoto,Marina;Rowsthorn,Ella;Cribb,Lachlan;Bransby,Lisa;Buckley,Rachel;Yassi,Nawaf;Yiallourou,Stephanie;Brodtmann,Amy;Velakoulis,Dennis;Eratne,Dhamidhu;Hamilton,GarunS;Naughton,MatthewT;Lim,
短时间和长时间的睡眠都与未来痴呆症的风险增加有关[1，2]。过渡到长时间睡眠可能是正在进行的神经变性的标志[1]。然而，将短睡眠时间与痴呆风险联系起来的机制尚不清楚;短睡眠时间可能通过限制胶质淋巴清除的机会而与阿尔茨海默病（AD）病理学直接相关[3]，或者可能通过共同的风险因素（如高血压[4]或AD的遗传易感性[5]）与独立于AD病理学的痴呆相关。在一项老年人研究中，自我报告的短睡眠时间（≤ 6 vs. 7-8 h）与正电子发射断层扫描（PET）测量的较高淀粉样蛋白β（Aβ）负荷相关[6]。然而，未检查其他AD生物标志物（例如tau）。由于睡眠和AD之间的关联可能是双向的，因此在年轻的认知未受损个体中建立这些关系非常重要，以确定睡眠时间与最早AD生物标志物变化相关的程度。这项初步研究的目的是检查夜间睡眠时间短是否与淀粉样蛋白，tau蛋白和神经变性（A/T/N）脑脊液（CSF）AD生物标志物相关，这些生物标志物以社区为基础，由有痴呆家族史的中年人组成。我们假设睡眠时间缩短与Aβ42降低（随着AD生物标志物严重程度的增加而降低）[7]和总tau、磷酸化tau 181（p-tau）和神经丝轻链（NfL）水平升高相关。健康大脑项目（HBP）是一项以社区为基础的研究，通过年度在线评估跟踪澳大利亚人的认知健康。符合资格的参与者包括年龄在40-70岁之间，居住在澳大利亚，英语流利的人。参与者是通过社交媒体和广告等各种来源自我推荐和招募的。共有82名参与者完成了生物标志物子研究，包括腰椎穿刺和2周的活动记录。排除了自我报告的认知障碍，神经退行性疾病或痴呆的参与者，以及那些服用痴呆或AD药物的参与者。该队列被富集以过度代表APOE ε4携带者（38%），66名参与者完成了所有测量并被纳入研究。该研究得到了墨尔本健康人类研究伦理委员会的批准。在皇家墨尔本医院（澳大利亚）通过L3/L4或L4/L5间隙的单次腰椎穿刺获得CSF样本，进行处理并在− 80º下储存。使用Roche Elecsys免疫测定法对解冻CSF中的Aβ42、t-tau和p-tau 181进行生化分析，而使用ELISA（UmanDiagnostics）测量NfL（神经变性的非特异性标志物）。进行所有生化分析
Both short and long sleep durations have been associated with an increased risk of future dementia [1, 2]. Transitioning to long sleep duration may be a marker of ongoing neurodegeneration [1]. However, the mechanisms linking short sleep time to dementia risk are unclear; short sleep duration may directly relate to Alzheimer’s Disease (AD) pathology by limiting the opportunity for glymphatic clearance [3], or may associate with dementia independent of AD pathology through shared risk factors, such as hypertension [4] or genetic vulnerability for AD [5]. In a study of older adults, self-reported short sleep duration (≤ 6 vs. 7–8 h) was associated with higher amyloid beta (Aβ) burden measured by positron emission tomography (PET) scans [6]. However, other AD biomarkers (eg tau) were not examined. Since associations between sleep and AD may be bidirectional, it is important to establish these relationships in younger cognitively unimpaired individuals, to determine the extent to which sleep time is associated with the earliest AD biomarker changes. This preliminary study aimed to examine if short nighttime sleep duration was associated with amyloid, tau, and neurodegeneration (A/T/N) cerebrospinal fluid (CSF) biomarkers of AD in a community-based cohort of middle-aged adults with a family history of dementia. We hypothesized that shorter sleep would be associated with lower Aβ42 (which decreases with increasing AD biomarker severity)[7] and higher total-tau, phosphorylated-tau 181 (p-tau), and neurofilament light chain (NfL) levels. The Healthy Brain Project (HBP) is a community-based study that tracks the cognitive health of Australians with annual online assessments [8]. Eligible participants include those aged 40–70 years, residing in Australia, and fluent in English. Participants were self-referred and recruited through various sources, such as social media and advertisements. A total of 82 participants completed a biomarker sub-study, including a lumbar puncture and 2 weeks of actigraphy. Participants with self-reported cognitive impairment, neurodegenerative disease, or dementia were excluded, as were those taking medications for dementia or AD. The cohort was enriched to over-represent APOE ε4 carriers (38%) and 66 participants completed all measures and were included in the study. The study was approved by the Melbourne Health Human Research Ethics Committee. CSF samples were obtained by single pass lumbar puncture in the L3/L4 or L4/L5 interspace at the Royal Melbourne Hospital (Australia), processed, and stored at− 80º. The biochemical analyses of Aβ42, t-tau, and p-tau181 from thawed CSF were conducted using the Roche Elecsys immunoassay, whereas NfL (a nonspecific marker of neurodegeneration) was measured using ELISA (UmanDiagnostics). All biochemical analyses were performed