Elevated Monoamine Oxidase-A in Anterior Cingulate of Post-Mortem Human Parkinson's Disease: A Potential Surrogate Biomarker for Lewy Bodies?
Elevated Monoamine Oxidase-A in Anterior Cingulate of Post-Mortem Human Parkinson's Disease: A Potential Surrogate Biomarker for Lewy Bodies?
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路易体（LB）在帕金森病（PD）中发挥神经病理学作用。我们的目标是使用抗泛素免疫组织化学（UIHC）评估LB，并使用成像剂[18 F] FAZIN 3找到与单胺氧化酶-A（MAO-A）的相关性。对来自对照受试者（CN）（n = 6，年龄81-90，LB = 0）和PD（n = 6，年龄77-89，LB = III-IV）的人死后前扣带回（AC）和胼胝体（CC）进行切片（10 μm切片）。用LB的抗泛素（UIHC）对脑切片进行免疫染色，并使用QuPath分析每单位面积（μm2）的抗泛素百分比。将相邻脑切片与[18 F] FAZIN 3孵育，并定量皮质层I-III、IV-VI和CC（白色物质）区域的[18 F] FAZIN 3结合。UIHC与[18 F] FAZIN 3结合相关。所有PD脑均为阳性UIHC染色，并证实存在LB。PD AC的外皮质层（I-III）具有21%的UIHC，而内层（IV-VI）具有>75%的UIHC。在CN脑中，LB不存在（<1%UIHC）。在所有PD受试者中观察到AC中与MAO-A结合的[18 F] FAZIN 3增加。PD受试者的[18 F] FAZIN 3比值为AC/CC = 3.57，而CN受试者的[18 F] FAZIN 3比值为AC/CC = 2.24。UIHC μm2的增加与[18 F] FAZIN 3与MAO-A的结合（DLU/mm 2）相关。在PD中增加的[18 F] FAZIN 3与MAO-A的结合是一种潜在的新型“热点”PET成像方法。
Lewy bodies (LB) play a neuropathological role in Parkinson’s disease (PD). Our goal was to evaluate LB using anti-ubiquitin immunohistochemistry (UIHC) and find correlations with monoamine oxidase-A (MAO-A) using imaging agent, [18F]FAZIN3. Human post-mortem anterior cingulate (AC) and corpus callosum (CC) from control subjects (CN), n = 6; age 81–90 LB = 0 and PD, n = 6, age 77–89, LB = III–IV were sectioned (10 μm slices). Brain slices were immunostained with anti-ubiquitin for LB (UIHC) and analyzed using QuPath for percent anti-ubiquitin per unit area (μm2). Adjacent brain slices were incubated with [18F]FAZIN3 and cortical layers I–III, IV–VI and CC (white matter) regions were quantified for the binding of [18F]FAZIN3. UIHC was correlated with [18F]FAZIN3 binding. All PD brains were positively UIHC stained and confirmed presence of LB. Outer cortical layers (I–III) of PD AC had 21% UIHC while inner layers (IV–VI) had >75% UIHC. In the CN brains LB were absent (<1% UIHC). Increased [18F]FAZIN3 binding to MAO-A in AC was observed in all PD subjects. [18F]FAZIN3 ratio in PD was AC/CC = 3.57 while in CN subjects it was AC/CC = 2.24. Increases in UIHC μm2 correlated with [18F]FAZIN3 binding to MAO-A in DLU/mm2. Increased [18F]FAZIN3 binding to MAO-A in PD is a potential novel “hot spot” PET imaging approach.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
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Sierecki E
影响因子：
3.1
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Gatley, SJ
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