Punsoni Michael, Friedman Joseph H, Resnick Murray, Donahue John E, Yang Dong Fang, Stopa Edward G
Department of Pathology.
Neurology, Rhode Island Hospital, Providence, RI.
Appl Immunohistochem Mol Morphol. 2019 Aug;27(7):543-548. doi: 10.1097/PAI.0000000000000613.
Gastrointestinal (GI) symptoms are common in Parkinson disease (PD), often preceding neurological manifestations; however, early diagnostic utility of GI biopsies remains controversial. Studies suggest aberrant deposition of alpha-synuclein (α-syn) follows step-wise progression in central nervous system though histologic interpretation of normal and aberrant staining patterns have shown variable results. This study examines whether GI α-syn mRNA expression combined with standard α-syn immunohistochemical staining enhance the role of GI biopsy in PD.
Four groups were examined, including pediatric (21) and adult control patients (18), PD clinic patients (17), and pathologically confirmed PD cases from hospital archives (16). Enteric nervous system α-syn staining was evaluated by immunohistochemistry in 33 PD and 39 controls. α-Syn mRNA levels were compared between patient groups using quantitative polymerase chain reaction and stomach and colon levels in PD.
PD patients had Lewy bodies (LB) and diffuse neuronal α-syn staining. GI tissues from elderly controls, children, and young adults exhibited diffuse positivity. LB were limited to PD. Myenteric plexus immunoreactivity varied in different regions. Widespread staining was noted within stomach and colon. Immunoreactivity was present within esophagus, appendix, and small bowel. α-Syn mRNA expression was highest in PD; however, levels varied between proximal and distal GI tract.
α-Syn is normally present within young and elderly enteric nervous system; furthermore, while α-syn mRNA is always detectable, levels are highest and most variable in PD. This suggests that enteric α-syn may be altered in neurodegenerative disease. The presence of LB in the GI tract, not solely α-syn expression, may prove useful, distinguishing neurodegenerative disease patients from normal controls.
胃肠道（GI）症状在帕金森病（PD）中很常见，通常先于神经学表现出现；然而，胃肠道活检的早期诊断效用仍存在争议。研究表明，α-突触核蛋白（α-syn）的异常沉积在中枢神经系统中呈逐步进展，尽管对正常和异常染色模式的组织学解释结果不一。本研究探讨胃肠道α-syn mRNA表达与标准α-syn免疫组化染色相结合是否能增强胃肠道活检在帕金森病中的作用。
研究对象分为四组，包括儿科对照患者（21例）、成人对照患者（18例）、帕金森病门诊患者（17例）以及来自医院档案中经病理确诊的帕金森病病例（16例）。通过免疫组化对33例帕金森病患者和39例对照者的肠神经系统α-syn染色进行评估。使用定量聚合酶链反应比较患者组之间的α-syn mRNA水平，并比较帕金森病患者胃和结肠中的水平。
帕金森病患者有路易小体（LB）和弥漫性神经元α-syn染色。老年对照者、儿童和年轻人的胃肠道组织呈现弥漫性阳性。路易小体仅限于帕金森病患者。肌间神经丛免疫反应性在不同区域有所不同。在胃和结肠内可见广泛染色。在食管、阑尾和小肠内也有免疫反应性。α-syn mRNA表达在帕金森病患者中最高；然而，胃肠道近端和远端的水平有所不同。
α-syn正常存在于年轻人和老年人的肠神经系统中；此外，虽然总能检测到α-syn mRNA，但在帕金森病中其水平最高且变化最大。这表明肠道α-syn可能在神经退行性疾病中发生改变。胃肠道中路易小体的存在，而非单纯的α-syn表达，可能有助于将神经退行性疾病患者与正常对照者区分开来。
