人死后帕金森病患者前扣带回中单胺氧化酶-A 升高：路易体的潜在替代生物标志物？
Elevated Monoamine Oxidase-A in Anterior Cingulate of Post-Mortem Human Parkinson's Disease: A Potential Surrogate Biomarker for Lewy Bodies?
机构信息
Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA.
出版信息
Cells. 2022 Dec 10;11(24):4000. doi: 10.3390/cells11244000.
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, [F]FAZIN3. Human post-mortem anterior cingulate (AC) and corpus callosum (CC) from control subjects (CN), = 6; age 81-90 LB = 0 and PD, = 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 (μm). Adjacent brain slices were incubated with [F]FAZIN3 and cortical layers I-III, IV-VI and CC (white matter) regions were quantified for the binding of [F]FAZIN3. UIHC was correlated with [F]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 [F]FAZIN3 binding to MAO-A in AC was observed in all PD subjects. [F]FAZIN3 ratio in PD was AC/CC = 3.57 while in CN subjects it was AC/CC = 2.24. Increases in UIHC μm correlated with [F]FAZIN3 binding to MAO-A in DLU/mm. Increased [F]FAZIN3 binding to MAO-A in PD is a potential novel "hot spot" PET imaging approach.
路易体（LB）在帕金森病（PD）中具有神经病理学作用。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 [F]FAZIN3 寻找与单胺氧化酶-A（MAO-A）的相关性。从对照受试者（CN）、年龄 81-90 岁 LB = 0 和 PD、年龄 77-89 岁 LB = III-IV 的人死后前扣带回（AC）和胼胝体（CC）获取脑切片（10 μm 切片）。用抗泛素对脑切片进行免疫染色，用于 LB（UIHC），并使用 QuPath 分析单位面积（μm）的抗泛素百分比。用 [F]FAZIN3 孵育相邻脑切片，并对皮质层 I-III、IV-VI 和 CC（白质）区域的 [F]FAZIN3 结合进行定量。UIHC 与 [F]FAZIN3 结合相关。所有 PD 脑均呈阳性 UIHC 染色，证实存在 LB。PD AC 的外皮质层（I-III）的 UIHC 为 21%，而内皮质层（IV-VI）的 UIHC >75%。在 CN 大脑中 LB 不存在（<1% UIHC）。在所有 PD 受试者中，AC 中 MAO-A 的 [F]FAZIN3 结合增加。PD 的 [F]FAZIN3 比值为 AC/CC = 3.57，而 CN 受试者的比值为 AC/CC = 2.24。UIHC μm 的增加与 DLU/mm 中 MAO-A 的 [F]FAZIN3 结合相关。PD 中 MAO-A 的 [F]FAZIN3 结合增加是一种潜在的新型“热点”PET 成像方法。
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