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The combined effect of amyloid-β and tau biomarkers on brain atrophy in dementia with Lewy bodies.
NeuroImage: Clinical ( IF 4.2 ) Pub Date : 2020-07-02 , DOI: 10.1016/j.nicl.2020.102333
Carla Abdelnour 1 , Daniel Ferreira 2 , Ketil Oppedal 3 , Lena Cavallin 4 , Olivier Bousiges 5 , Lars Olof Wahlund 2 , Jakub Hort 6 , Zuzana Nedelska 6 , Alessandro Padovani 7 , Andrea Pilotto 7 , Laura Bonanni 8 , Milica G Kramberger 9 , Mercè Boada 10 , Eric Westman 11 , Javier Pagonabarraga 12 , Jaime Kulisevsky 12 , Frédéric Blanc 13 , Dag Aarsland 14
Affiliation  

Background

Alzheimer’s disease (AD)-related pathology is frequently found in patients with dementia with Lewy bodies (DLB). However, it is unknown how amyloid-β and tau-related pathologies influence neurodegeneration in DLB. Understanding the mechanisms underlying brain atrophy in DLB can improve our knowledge about disease progression, differential diagnosis, drug development and testing of anti-amyloid and anti-tau therapies in DLB.

Objectives

We aimed at investigating the combined effect of CSF amyloid-β42, phosphorylated tau and total tau on regional brain atrophy in DLB in the European DLB (E-DLB) cohort.

Methods

86 probable DLB patients from the E-DLB cohort with CSF and MRI data were included. Random forest was used to analyze the association of CSF biomarkers (predictors) with visual rating scales for medial temporal lobe atrophy (MTA), posterior atrophy (PA) and global cortical atrophy scale-frontal subscale (GCA-F) (outcomes), including age, sex, education and disease duration as extra predictors.

Results

DLB patients with abnormal MTA scores had abnormal CSF Aβ42, shorter disease duration and older age. DLB patients with abnormal PA scores had abnormal levels of CSF Aβ42 and p-tau, older age, lower education and shorter disease duration. Abnormal GCA-F scores were associated with lower education, male sex, and older age, but not with any AD-related CSF biomarker.

Conclusions

This study shows preliminary data on the potential combined effect of amyloid-β and tau-related pathologies on the integrity of posterior brain cortices in DLB patients, whereas only amyloid-β seems to be related to MTA. Future availability of α-synuclein biomarkers will help us to understand the effect of α-synuclein and AD-related pathologies on brain integrity in DLB.



中文翻译:

β-淀粉样蛋白和tau生物标志物对路易小体痴呆患者脑萎缩的联合作用。

背景

与路易体痴呆(DLB)的患者经常发现与阿尔茨海默病(AD)相关的病理。但是,尚不清楚淀粉样蛋白-β和tau相关病理如何影响DLB中的神经变性。了解DLB中脑萎缩的潜在机制可以改善我们对DLB中疾病进展,鉴别诊断,药物开发以及抗淀粉样蛋白和抗tau疗法的测试的了解。

目标

我们旨在研究欧洲DLB(E-DLB)队列中CSF淀粉样蛋白β42,磷酸化tau和总tau对DLB区域脑萎缩的联合作用。

方法

包括来自E-DLB队列的86名可能具有CSF和MRI数据的DLB患者。随机森林被用来分析脑脊液生物标志物(预测因子)与内侧颞叶萎缩(MTA),后部萎缩(PA)和整体皮层萎缩量表-额叶副量表(GCA-F)(结果)的视觉评分量表的关联,包括年龄,性别,教育程度和疾病持续时间是额外的预测指标。

结果

MTA评分异常的DLB患者脑脊液Aβ42异常,病程短,年龄大。PA评分异常的DLB患者的CSFAβ42和p-tau水平异常,年龄较大,受教育程度较低,病程较短。GCA-F评分异常与低学历,男性和老年人有关,但与任何与AD相关的CSF生物标志物均无关。

结论

这项研究显示了有关DLB患者淀粉样蛋白β和tau相关病理学对后脑皮质完整性的潜在联合作用的初步数据,而只有淀粉样蛋白β似乎与MTA相关。α-突触核蛋白生物标记物的未来可用性将帮助我们了解α-突触核蛋白和AD相关病理学对DLB脑完整性的影响。

更新日期:2020-07-13
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