淀粉样蛋白示踪剂在常染色体显性遗传和散发性阿尔茨海默病中的结合部位。
Amyloid tracers binding sites in autosomal dominant and sporadic Alzheimer's disease.
机构信息
Division of Translational Alzheimer Neurobiology, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
Division of Clinical Geriatrics, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, University of Oslo, Oslo, Norway.
出版信息
Alzheimers Dement. 2017 Apr;13(4):419-430. doi: 10.1016/j.jalz.2016.08.006. Epub 2016 Sep 28.
INTRODUCTION
Amyloid imaging has been integrated into diagnostic criteria for Alzheimer's disease (AD). How amyloid tracers binding differ for different tracer structures and amyloid-β aggregates in autosomal dominant AD (ADAD) and sporadic AD is unclear.
METHODS
Binding properties of different amyloid tracers were examined in brain homogenates from six ADAD with APPswe, PS1 M146V, and PS1 EΔ9 mutations, 13 sporadic AD, and 14 control cases.
RESULTS
H-PIB, H-florbetaben, H-AZD2184, and BTA-1 shared a high- and a varying low-affinity binding site in the frontal cortex of sporadic AD. AZD2184 detected another binding site (affinity 33 nM) in the frontal cortex of ADAD. The H-AZD2184 and H-PIB binding were significantly higher in the striatum of ADAD compared to sporadic AD and control. Polyphenol resveratrol showed strongest inhibition on H-AZD84 binding followed by H-florbetaben and minimal on H-PIB.
DISCUSSION
This study implies amyloid tracers of different structures detect different sites on amyloid-β fibrils or conformations.
简介
淀粉样蛋白成像已被纳入阿尔茨海默病（AD）的诊断标准。然而，对于常染色体显性 AD（ADAD）和散发性 AD 中不同示踪剂结构和淀粉样β聚集物的结合方式，我们还不是很清楚。
方法
我们检测了 6 例具有 APPswe、PS1 M146V 和 PS1 EΔ9 突变的 ADAD、13 例散发性 AD 和 14 例对照病例的脑匀浆中不同淀粉样蛋白示踪剂的结合特性。
结果
H-PIB、H-florbetaben、H-AZD2184 和 BTA-1 在散发性 AD 的额叶皮层中具有高亲和性和可变的低亲和性结合位点。AZD2184 在 ADAD 的额叶皮层中检测到另一个结合位点（亲和力为 33 nM）。与散发性 AD 和对照组相比，ADAD 的纹状体中 H-AZD2184 和 H-PIB 的结合明显更高。多酚白藜芦醇对 H-AZD84 结合的抑制作用最强，其次是 H-florbetaben，对 H-PIB 的抑制作用最小。
讨论
本研究表明，不同结构的淀粉样蛋白示踪剂检测到淀粉样β纤维或构象上的不同部位。
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