Incidental Lewy body disease and preclinical Parkinson disease
Incidental Lewy body disease and preclinical Parkinson disease
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DOI：
10.1001/archneur.65.8.1074
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发表时间：
2008-08-01
影响因子：
--
通讯作者：
Dickson, Dennis W.
中科院分区：
文献类型：
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作者：
DelleDonne, Anthony;Klos, Kevin J.;Dickson, Dennis W.
工作背景：在临床正常个体的脑中尸检时检测到的路易体的意义尚不确定，但可能代表临床前帕金森病（PD）。目的：为了确定偶然性路易体病（iLBD）是否存在纹状体多巴胺能神经支配减少和黑质细胞丢失，因为人们可能会期望它是否是PD的前兆。设计：病例对照研究。设置：从三级医学中心获得医疗记录和存档脑组织用于进一步研究。参与者：来自60岁以上具有α-突触核蛋白免疫反应性Lewy小体的临床健康个体的脑将iLBD（n=12）与来自无α-突触核蛋白病理学发现的临床健康个体（n=31）和患有PD的患者（n=25）的那些进行比较。纹状体多巴胺能的完整性通过酪氨酸羟化酶（TH）和囊泡单胺转运蛋白2（VMAT 2）的免疫荧光、黑质神经元损失评分和根据PD分期的路易体分布在壳核切片中进行评估。与病理正常的受试者相比，在患有iLBD的受试者中，记录了纹状体多巴胺能免疫反应性降低的TH（33%）和VMAT 2（42%）;正如所预期的，PD的降低甚至更大（TH降低73%，VMAT 2降低96%）。黑质神经元丢失与纹状体TH（r=-0.84）和VMAT 2（r=-0.77）均呈负相关。PD分期与纹状体VMAT 2（r=-0.85）和TH（r=-0.85）呈负相关。结论：iLBD患者黑质-纹状体病理特征介于病理正常人和PD患者之间。研究结果表明，iLBD可能代表症状前PD，而不是非特异性的，年龄相关的α-突触核蛋白的病理变化。
Background: The significance of Lewy bodies detected at autopsy in the brains of clinically normal individuals is uncertain but may represent preclinical Parkinson disease (PD).Objective: To determine whether diminished striatal dopaminergic innervation and nigral cell loss are present in incidental Lewy body disease (iLBD), as one might expect if it is a forerunner of PD.Design: Case-control study.Setting: Medical records and archival brain tissue were obtained from a tertiary medical center for further study.Participants: Brains from clinically healthy individuals older than 60 years with alpha-synuclein-immunoreactive Lewy bodies (iLBD; n=12) were compared with those from clinically healthy individuals with no alpha-synuclein pathologic findings (n=31) and patients with PD (n=25).Main Outcome Measures: Striatal dopaminergic integrity assessed in sections of putamen by immunofluorescence for tyrosine hydroxylase (TH) and vesicular monoamine transporter 2 (VMAT2), neuronal loss score in the substantia nigra, and distribution of Lewy bodies according to PD stage.Results: Among the participants with iLBD, decreased striatal dopaminergic immunoreactivity was documented for both TH (33%) and VMAT2 (42%), compared with the pathologically normal subjects; as expected, the reductions were even greater in PD (73% decrease for TH and 96% decrease for VMAT2). Substantia nigra neuronal loss inversely correlated with both striatal TH (r=-0.84) and VMAT2 (r=-0.77). In addition, PD stage inversely correlated with both striatal VMAT2 (r=-0.85) and TH (r=-0.85).Conclusions: The results indicate that iLBD has nigro-striatal pathological features that are intermediate between those in pathologically normal persons and those with PD. The findings suggest that iLBD probably represents presymptomatic PD, rather than nonspecific, age-related alpha-synuclein pathological changes.