Queen Square Brain Bank for Neurological Disorders, London, UK.
J Parkinsons Dis. 2011;1(3):277-86. doi: 10.3233/JPD-2011-11046.
Progressive rostral spread of Lewy body (LB) pathology is thought to reflect the clinical course of Parkinson's disease (PD) although several studies have suggested that LBs are not the toxic species responsible for cell death. We investigated the relationship between nigral dopaminergic cell loss, distribution and density of α-synuclein-immunoreactive LBs and duration of motor symptoms in 97 patients with PD. Density of pigmented neurons was measured in a single section of one half of the substantia nigra (SN) with delineation of the dorsal and ventral tiers whereas the cortical and nigral LB densities were determined using a morphometric approach. The density of nigral neurons was estimated to decrease by 2% each year after confirmation of the clinical diagnosis of PD but showed marked heterogeneity with some PD patients with longer duration of illness still possessing a significant number of preserved pigmented nigral neurons at the time of death. An average 15% of surviving nigral neurones contained LBs and the age-adjusted proportion of LB-bearing neurons appeared relatively stable throughout the disease duration. No difference was observed in the age at death or duration of disease with respect to Braak PD stages. The nigral neuronal density was unrelated to either the Braak PD stage or to cortical LB densities. We conclude that nigral neuronal loss is slow and shows considerable variation in PD. Our data also provides no support for a primary pathogenic role of LBs as neither their distribution nor density was associated with the severity of nigral cell loss.
路易小体（LB）病理的进行性向喙侧扩散被认为反映了帕金森病（PD）的临床病程，尽管一些研究表明路易小体并非导致细胞死亡的毒性物质。我们调查了97例PD患者中黑质多巴胺能细胞丢失、α-突触核蛋白免疫反应性路易小体的分布和密度与运动症状持续时间之间的关系。在黑质（SN）一半的单个切片中测量色素神经元的密度，并划分背侧和腹侧层，而皮质和黑质路易小体密度则采用形态计量学方法确定。在确诊PD临床诊断后，估计黑质神经元密度每年下降2%，但显示出明显的异质性，一些病程较长的PD患者在死亡时仍有大量保存的色素性黑质神经元。平均15%存活的黑质神经元含有路易小体，且在整个疾病过程中，经年龄调整的含路易小体神经元比例相对稳定。在死亡年龄或疾病持续时间方面，未观察到与Braak PD分期相关的差异。黑质神经元密度与Braak PD分期或皮质路易小体密度均无关。我们得出结论，黑质神经元丢失缓慢，在PD中表现出相当大的变异性。我们的数据也不支持路易小体的主要致病作用，因为它们的分布和密度均与黑质细胞丢失的严重程度无关。
