血浆淀粉样蛋白-β水平、脑萎缩与痴呆风险：一项基于人群的研究。
Plasma amyloid-β levels, cerebral atrophy and risk of dementia: a population-based study.
机构信息
Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Office no. 2505, Wytemaweg 80, 3015, CN, Rotterdam, The Netherlands.
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
出版信息
Alzheimers Res Ther. 2018 Jun 30;10(1):63. doi: 10.1186/s13195-018-0395-6.
BACKGROUND
Plasma amyloid-β (Aβ) levels are increasingly studied as a potential accessible marker of cognitive impairment and dementia. However, it remains underexplored whether plasma Aβ levels including the novel Aβ peptide 1-38 (Aβ) relate to preclinical markers of neurodegeneration and risk of dementia. We investigated the association of plasma Aβ, Aβ, and Aβ levels with imaging markers of neurodegeneration and risk of dementia in a prospective population-based study.
METHODS
We analyzed plasma Aβ levels in 458 individuals from the Rotterdam Study. Brain volumes, including gray matter, white matter, and hippocampus, were computed on the basis of 1.5-T magnetic resonance imaging (MRI). Dementia and its subtypes were defined on the basis of internationally accepted criteria.
RESULTS
A total of 458 individuals (mean age, 67.8 ± 7.7 yr; 232 [50.7%] women) with baseline MRI scans and incident dementia were included. The mean ± SD values of Aβ, Aβ, and Aβ (in pg/ml) were 19.4 ± 4.3, 186.1 ± 35.9, and 56.3 ± 6.2, respectively, at baseline. Lower plasma Aβ levels were associated with smaller hippocampal volume (mean difference in hippocampal volume per SD decrease in Aβ levels, - 0.13; 95% CI, - 0.23 to - 0.04; p = 0.007). After a mean follow-up of 14.8 years (SD, 4.9; range, 4.1-23.5 yr), 79 persons developed dementia, 64 of whom were diagnosed with Alzheimer's disease (AD). Lower levels of Aβ and Aβ were associated with increased risk of dementia, specifically AD (HR for AD per SD decrease in Aβ levels, 1.39; 95% CI, 1.00-2.16; HR for AD per SD decrease in Aβ levels, 1.35; 95% CI, 1.05-1.75) after adjustment for age, sex, education, cardiovascular risk factors, apolipoprotein E ε4 allele carrier status, and other Aβ isoforms.
CONCLUSIONS
Our results show that lower plasma Aβ levels were associated with risk of dementia and incident AD. Moreover, lower plasma Aβ levels were related to smaller hippocampal volume. These results suggest that plasma Aβ and Aβ maybe useful biomarkers for identification of individuals at risk of dementia.
背景
血浆淀粉样蛋白-β（Aβ）水平作为认知障碍和痴呆的潜在可及标志物，其研究日益增多。然而，目前仍不清楚包括新型 Aβ 肽 1-38（Aβ）在内的血浆 Aβ 水平是否与神经退行性变的临床前标志物和痴呆风险相关。我们在一项前瞻性人群研究中调查了血浆 Aβ、Aβ 和 Aβ 水平与神经退行性变的影像学标志物和痴呆风险之间的关联。
方法
我们分析了 Rotterdam 研究中 458 名个体的血浆 Aβ 水平。基于 1.5-T 磁共振成像（MRI）计算脑容量，包括灰质、白质和海马体。痴呆及其亚型根据国际公认的标准定义。
结果
共纳入 458 名基线 MRI 扫描和新发痴呆的个体（平均年龄 67.8 ± 7.7 岁；232 [50.7%] 名女性）。基线时 Aβ、Aβ 和 Aβ（pg/ml）的平均值 ± 标准差分别为 19.4 ± 4.3、186.1 ± 35.9 和 56.3 ± 6.2。血浆 Aβ 水平较低与海马体体积较小相关（Aβ 水平每降低一个标准差，海马体体积平均差异-0.13；95%CI，-0.23 至-0.04；p=0.007）。平均随访 14.8 年后（SD，4.9；范围，4.1-23.5 年），79 人发生痴呆，其中 64 人被诊断为阿尔茨海默病（AD）。Aβ 和 Aβ 水平降低与痴呆风险增加相关，特别是 AD（Aβ 水平每降低一个标准差，AD 的 HR，1.39；95%CI，1.00-2.16；Aβ 水平每降低一个标准差，AD 的 HR，1.35；95%CI，1.05-1.75），调整年龄、性别、教育程度、心血管危险因素、载脂蛋白 E ε4 等位基因状态和其他 Aβ 同工型后。
结论
我们的结果表明，血浆 Aβ 水平较低与痴呆和 AD 的发病风险相关。此外，较低的血浆 Aβ 水平与较小的海马体体积有关。这些结果表明，血浆 Aβ 和 Aβ 可能是识别痴呆风险个体的有用生物标志物。
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