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临床病理相关性:通过神经病理学对 3 名临床诊断为阿尔茨海默病或路易体痴呆症的患者进行多巴胺和淀粉样蛋白 PET 成像。

Clinicopathological Correlation: Dopamine and Amyloid PET Imaging with Neuropathology in Three Subjects Clinically Diagnosed with Alzheimer's Disease or Dementia with Lewy Bodies.

机构信息

Department of Neurology, The University of Kansas Health System, Kansas City, KS, USA.

Banner Sun Health Research Institute, Sun City, AZ, USA.

出版信息

J Alzheimers Dis. 2021;80(4):1603-1612. doi: 10.3233/JAD-200323.

Abstract

BACKGROUND

Imaging biomarkers have the potential to distinguish between different brain pathologies based on the type of ligand used with PET. AV-45 PET (florbetapir, Amyvid™) is selective for the neuritic plaque amyloid of Alzheimer's disease (AD), while AV-133 PET (florbenazine) is selective for VMAT2, which is a dopaminergic marker.

OBJECTIVE

To report the clinical, AV-133 PET, AV-45 PET, and neuropathological findings of three clinically diagnosed dementia patients who were part of the Avid Radiopharmaceuticals AV133-B03 study as well as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND).

METHODS

Three subjects who had PET imaging with both AV-133 and AV-45 as well as a standardized neuropathological assessment were included. The final clinical, PET scan, and neuropathological diagnoses were compared.

RESULTS

The clinical and neuropathological diagnoses were made blinded to PET scan results. The first subject had a clinical diagnosis of dementia with Lewy bodies (DLB); AV-133 PET showed bilateral striatal dopaminergic degeneration, and AV-45 PET was positive for amyloid. The final clinicopathological diagnosis was DLB and AD. The second subject was diagnosed clinically with probable AD; AV-45 PET was positive for amyloid, while striatal AV-133 PET was normal. The final clinicopathological diagnosis was DLB and AD. The third subject had a clinical diagnosis of DLB. Her AV-45 PET was positive for amyloid and striatal AV-133 showed dopaminergic degeneration. The final clinicopathological diagnosis was multiple system atrophy and AD.

CONCLUSION

PET imaging using AV-133 for the assessment of striatal VMAT2 density may help distinguish between AD and DLB. However, some cases of DLB with less-pronounced nigrostriatal dopaminergic neuronal loss may be missed.

摘要

背景

成像生物标志物有可能根据正电子发射断层扫描(PET)使用的配体类型来区分不同的脑部病变。AV-45 PET(florbetapir,Amyvid)对阿尔茨海默病(AD)的神经纤维缠结淀粉样蛋白具有选择性,而 AV-133 PET(florbenazine)对 VMAT2 具有选择性,VMAT2 是一种多巴胺能标志物。

目的

报告 3 例经临床诊断为痴呆的患者的临床、AV-133 PET、AV-45 PET 和神经病理学检查结果,这些患者是 Avid Radiopharmaceuticals AV133-B03 研究以及亚利桑那州衰老和神经退行性疾病研究(AZSAND)的一部分。

方法

纳入了 3 例接受 AV-133 和 AV-45 正电子发射断层扫描成像以及标准化神经病理学评估的患者。比较了最终的临床、PET 扫描和神经病理学诊断。

结果

临床和神经病理学诊断是在不了解 PET 扫描结果的情况下做出的。第一位患者的临床诊断为路易体痴呆(DLB);AV-133 PET 显示双侧纹状体多巴胺能变性,AV-45 PET 淀粉样蛋白阳性。最终的临床病理诊断为 DLB 和 AD。第二位患者的临床诊断为可能的 AD;AV-45 PET 淀粉样蛋白阳性,而纹状体 AV-133 PET 正常。最终的临床病理诊断为 DLB 和 AD。第三位患者的临床诊断为 DLB。她的 AV-45 PET 淀粉样蛋白阳性,而纹状体 AV-133 显示多巴胺能变性。最终的临床病理诊断为多系统萎缩和 AD。

结论

使用 AV-133 评估纹状体 VMAT2 密度的正电子发射断层扫描成像可能有助于区分 AD 和 DLB。然而,一些多巴胺能神经元丢失不明显的 DLB 病例可能会被遗漏。

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