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脉络丛体积与脑脊液蛋白水平相关:与阿尔茨海默病和帕金森病的关系。

Choroid plexus volume is associated with levels of CSF proteins: relevance for Alzheimer's and Parkinson's disease.

机构信息

Berenson-Allen Center for Non-Invasive Brain Stimulation and Division for Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Berenson-Allen Center for Non-Invasive Brain Stimulation and Division for Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Hinda and Arthur Marcus Institute for Aging Research and Center for Memory Health, Hebrew SeniorLife, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Guttmann Brain Health Institut, Guttmann Institut, Universitat Autonoma, Barcelona, Spain.

出版信息

Neurobiol Aging. 2020 May;89:108-117. doi: 10.1016/j.neurobiolaging.2020.01.005. Epub 2020 Jan 16.

Abstract

The choroid plexus (ChP) is a major source of cerebrospinal fluid (CSF) production, with a direct and indirect role in protein clearance, and pathogenesis of Alzheimer's disease (AD). Here, we tested the link between the ChP volume and levels of CSF proteins in 2 data sets of (i) healthy controls, mild cognitive impairment (MCI), and AD patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 509), and (ii) healthy controls and Parkinson's disease (PD) patients from the Parkinson's Progression Markers Initiative (N = 302). All patients had baseline CSF proteins (amyloid-β, total and phosphorylated-tau and α-synuclein (only in Parkinson's Progression Markers Initiative)). ChP was automatically segmented on 3T structural T1-weighted MRIs. We found negative associations between ChP volume and CSF proteins, which were stronger in healthy controls, early-MCI patients, and PD patients compared with late-MCI and AD patients. Further grouping of patients of ADNI dataset into amyloid-positive and amyloid-negative based on their florbetapir (AV45) PET imaging showed that the association between ChP volume and CSF proteins (t/p-tau) was lower in amyloid-positive group. Our findings support the possible role of ChP in the clearance of CSF proteins, provide evidence for ChP dysfunction in AD, and suggest the need to account for the ChP volume in future studies of CSF-based biomarkers.

摘要

脉络丛(ChP)是脑脊液(CSF)产生的主要来源,在蛋白质清除和阿尔茨海默病(AD)的发病机制中具有直接和间接作用。在这里,我们在两个数据集(i)来自阿尔茨海默病神经影像学倡议(ADNI)的健康对照组、轻度认知障碍(MCI)和 AD 患者(N=509)和(ii)来自帕金森病进展标志物倡议(N=302)的健康对照组和帕金森病患者中,测试了 ChP 体积与 CSF 蛋白水平之间的联系。所有患者均有基线 CSF 蛋白(淀粉样蛋白-β、总和磷酸化-tau 和 α-突触核蛋白(仅在帕金森病进展标志物倡议中))。在 3T 结构 T1 加权 MRI 上自动分割 ChP。我们发现 ChP 体积与 CSF 蛋白之间存在负相关,在健康对照组、早期 MCI 患者和 PD 患者中比晚期 MCI 和 AD 患者更强。进一步根据其 florbetapir(AV45)PET 成像将 ADNI 数据集的患者分为淀粉样蛋白阳性和淀粉样蛋白阴性组,结果表明 ChP 体积与 CSF 蛋白(t/p-tau)之间的相关性在淀粉样蛋白阳性组中较低。我们的发现支持 ChP 在 CSF 蛋白清除中的可能作用,为 AD 中 ChP 功能障碍提供了证据,并表明在未来基于 CSF 的生物标志物研究中需要考虑 ChP 体积。

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