The combined effect of amyloid-β and tau biomarkers on brain atrophy in dementia with Lewy bodies
The combined effect of amyloid-β and tau biomarkers on brain atrophy in dementia with Lewy bodies
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DOI：
10.1016/j.nicl.2020.102333
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发表时间：
2020-01-01
影响因子：
4.2
通讯作者：
Aarsland, Dag
中科院分区：
文献类型：
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作者：
Abdelnour, Carla;Ferreira, Daniel;Aarsland, Dag
背景：阿尔茨海默病(AD)相关病理常见于路易体痴呆(DLB)患者。然而，目前尚不清楚淀粉样β蛋白和tau相关的病理如何影响DLB中的神经变性。了解DLB脑萎缩的发病机制有助于提高我们对DLB脑萎缩的疾病进展、鉴别诊断、药物开发以及抗淀粉样蛋白和抗tau治疗试验的认识。目的：在欧洲DLB型队列中，研究脑脊液淀粉样β42、磷酸化tau和总tau对DLB局灶性脑萎缩的联合作用。结果：以年龄、性别、文化程度和病程作为额外预测因素，对内侧颞叶萎缩(MTA)、后部萎缩(PA)和整体皮质萎缩(GCA-F)量表(结果)进行脑脊液生物标志物(预测因子)与视觉评分的相关性分析。PA评分异常的DLB患者脑脊液Aβ42和p-tau水平异常，年龄大、文化程度低、病程短。GCA-F评分异常与受教育程度低、男性和年龄较大有关，但与任何AD相关的脑脊液生物标志物无关。结论：这项研究显示了淀粉样β蛋白和tau相关病理对DLB患者大脑后皮质完整性的潜在联合作用的初步数据，而似乎只有淀粉样β蛋白与MTA有关。未来α-突触核蛋白生物标志物的可获得性将有助于我们了解a-突触核蛋白和AD相关病理对DLB脑完整性的影响。
Background: Alzheimer's disease (AD)-related pathology is frequently found in patients with dementia with Lewy bodies (DLB). However, it is unknown how amyloid-beta 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-beta 42, 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 A beta 42, shorter disease duration and older age. DLB patients with abnormal PA scores had abnormal levels of CSF A beta 42 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-beta and tau-related pathologies on the integrity of posterior brain cortices in DLB patients, whereas only amyloid-beta seems to be related to MTA. Future availability of a-synuclein biomarkers will help us to understand the effect of a-synuclein and AD-related pathologies on brain integrity in DLB.