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Clinical and striatal dopamine transporter predictors of β-amyloid in dementia with Lewy bodies.

路易体痴呆 β-淀粉样蛋白的临床和纹状体多巴胺转运蛋白预测因子。

  • 影响因子:3.85
  • DOI:10.1212/WNL.0000000000009168
  • 作者列表:"Yoo HS","Lee S","Chung SJ","Lee YH","Ye BS","Sohn YH","Yun M","Lee PH
  • 发表时间:2020-02-21
Abstract

OBJECTIVE:To investigate the relationship between β-amyloid (Aβ) deposition and striatal dopamine depletion, cognitive functions, and neuropsychiatric symptoms in dementia with Lewy bodies (DLB). METHODS:We consecutively recruited 51 patients with DLB who had undergone a neuropsychological test, Neuropsychiatric Inventory assessment, brain MRI, N-(3-[18F]fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) PET, and 18F-florbetaben PET within 6 months. The patients were divided into Aβ-negative (DLB-Aβ-, n = 20) and Aβ-positive (DLB-Aβ+, n = 31) groups according to the brain amyloid plaque load score. We performed comparative analyses of dopamine transporter (DAT) activity, neuropsychological profile, and neuropsychiatric symptoms between the 2 groups. RESULTS:Compared to the DLB-Aβ- group, the DLB-Aβ+ group had a younger age at diagnosis (p = 0.017), poorer performance in attention (p = 0.028) and visuospatial (p = 0.006) functions, and higher proportion of anxiety (p = 0.006) and total neuropsychiatric burden (p = 0.013). Those in the DLB-Aβ+ group also had lower DAT activity in the anterior putamen (p = 0.015) and ventral striatum (p = 0.006) regardless of age, sex, and years of education. In addition, lower DAT activity in the ventral striatum was significantly associated with anxiety and total neuropsychiatric burden in DLB. CONCLUSIONS:This study demonstrated that Aβ deposition in DLB is associated with diagnosis at a younger age, higher cognitive and neuropsychiatric burden, and decreased DAT activity, suggesting that evaluation of clinical features and DAT activity can predict the presence of Aβ in DLB.

摘要

目的: 探讨路易体痴呆 (DLB) 患者 β-淀粉样蛋白 (a β) 沉积与纹状体多巴胺耗竭、认知功能及神经精神症状的关系。 方法: 我们连续招募了 51 例 DLB 患者,他们接受了神经心理测试、神经精神量表评估、脑 MRI 、 N-(3-[18F] 氟丙基)-2 β-碳乙氧基-3 β-(4-碘苯基) PET,以及 6 个月内的 18f-florbetaben PET。将患者分为 a β 阴性 (DLB-a β,n = 20) 和 a β 阳性 (DLB-a β +,n = 31) 各组根据脑淀粉样斑块负荷评分。我们对 2 组之间的多巴胺转运蛋白 (DAT) 活性、神经心理学特征和神经精神症状进行了比较分析。 结果: 与 DLB-a β 组相比,DLB-a β + 组诊断时年龄较小 (p = 0.017),注意力表现较差 (p = 0.028) 和视觉空间 (p = 0.006) 的功能,和较高的比例焦虑 (p = 0.006) 和总神经精神负担 (p = 0.013)。DLB-a β + 组的前壳核 (p = 0.015) 和腹侧纹状体 (p = 0.006) 的 DAT 活性也较低,与年龄、性别无关。和多年的教育。此外,腹侧纹状体中较低的 DAT 活性与 DLB 的焦虑和总神经精神负担显著相关。 结论: 本研究证明 DLB 中的 a β 沉积与年轻时的诊断、较高的认知和神经精神负担以及 DAT 活性降低有关, 提示评价临床特征和 DAT 活性可预测 DLB 中 a β 的存在。

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翻译标题与摘要 下载文献
影响因子:3.92
发表时间:2020-01-01
DOI:10.1111/bpa.12761
作者列表:["Sebastián-Serrano Á","Simón-García A","Belmonte-Alfaro A","Pose-Utrilla J","Santos-Galindo M","Del Puerto A","García-Guerra L","Hernández IH","Schiavo G","Campanero MR","Lucas JJ","Iglesias T"]

METHODS::Huntington's disease (HD) is an inherited progressive neurodegenerative disease characterized by brain atrophy particularly in the striatum that produces motor impairment, and cognitive and psychiatric disturbances. Multiple pathogenic mechanisms have been proposed including dysfunctions in neurotrophic support and calpain-overactivation, among others. Kinase D-interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), is an essential mediator of neurotrophin signaling. In adult brain, Kidins220 presents two main isoforms that differ in their carboxy-terminal length and critical protein-protein interaction domains. These variants are generated through alternative terminal exon splicing of the conventional exon 32 (Kidins220-C32) and the recently identified exon 33 (Kidins220-C33). The lack of domains encoded by exon 32 involved in key neuronal functions, including those controlling neurotrophin pathways, pointed to Kidins220-C33 as a form detrimental for neurons. However, the functional role of Kidins220-C33 in neurodegeneration or other pathologies, including HD, has not been explored. In the present work, we discover an unexpected selective downregulation of Kidins220-C33, in the striatum of HD patients, as well as in the R6/1 HD mouse model starting at early symptomatic stages. These changes are C33-specific as Kidins220-C32 variant remains unchanged. We also find the early decrease in Kidins220-C33 levels takes place in neurons, suggesting an unanticipated neuroprotective role for this isoform. Finally, using ex vivo assays and primary neurons, we demonstrate that Kidins220-C33 is downregulated by mechanisms that depend on the activation of the protease calpain. Altogether, these results strongly suggest that calpain-mediated Kidins220-C33 proteolysis modulates onset and/or progression of HD.

翻译标题与摘要 下载文献
影响因子:3.66
发表时间:2020-01-24
DOI:10.3233/JAD-191069
作者列表:["Mendes FR","Leclerc JL","Liu L","Kamat PK","Naziripour A","Hernandez D","Li C","Ahmad AS","Doré S"]

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