Jellinger Kurt A
Institute of Clinical Neurobiology, Kenyongasse 18, 1070 Vienna, Austria.
Acta Neuropathol. 2003 Sep;106(3):191-201. doi: 10.1007/s00401-003-0725-y. Epub 2003 Jul 5.
To study the incidence and topographic distribution of alpha-synuclein-positive inclusions in Parkinson's disease (PD), dementia with LB (DLB), and Alzheimer's disease (AD), 206 brains of elderly patients, including 53 patients with clinical PD, 110 autopsy-proven AD cases, 22 with dementia with LB (DLB), 1 case with essential tremor, and 20 age-matched controls were investigated using alpha-synuclein immunohistochemistry. For technical reasons, the olfactory system was not studied. In all PD brains, alpha-synuclein-positive inclusions and neuronal losses were present in medullary and pontine nuclei, locus coeruleus, and substantia nigra, with additional lesions in amygdala (24%), allocortex (58%), cingulate area (34%), and isocortex (26.5%). All PD cases corresponded to pathology stage 4-6 suggested by Braak et al. (2003, Neurobiol Aging 24:197). In most cases of DLB, the distribution of alpha-synuclein pathology and neurodegeneration corresponded to stages 5 and 6 of PD pathology. The case with essential tremor and 48.2% of the AD cases showed no LB pathology; in the other AD brains alpha-synuclein-positive inclusions were seen in various brain areas. None of the controls showed LB pathology. Among 12 cases of incidental Lewy body disease (without clinical parkinsonian signs), 7 corresponded morphologically to PD stage 3 or 4. In further 6 AD cases, 2 with parkinsonian symptoms, considerable damage to locus coeruleus, substantia nigra, nucleus basalis and allocortex with preservation of the medullary nuclei was seen. The preliminary data largely confirm the Braak staging of brain pathology, although some of the clinical PD cases corresponded to stage 3 often considered as "preclinical". In addition, some cases without demonstrable involvement of medullary nuclei showed extensive PD-like pathology in other brain areas, suggesting deviation from the proposed stereotypic expansion pattern and that incidental LB pathology may affect solely the locus coeruleus and substantia nigra. Striking similarity of LB pathology between DLB and PD suggests close morphological relationship between both disorders. Widespread LB lesions occurred in many sporadic AD cases without parkinsonian symptoms, the pathogenesis and clinical impact of which are unclear. The relationship between AD and PD with particular reference to alpha-synuclein-positive lesions needs further elucidation [corrected].
为研究帕金森病（PD）、路易体痴呆（DLB）和阿尔茨海默病（AD）中α-突触核蛋白阳性包涵体的发生率及部位分布，我们采用α-突触核蛋白免疫组化方法，对206例老年患者的脑标本进行了研究，其中包括53例临床诊断为PD的患者、110例经尸检证实的AD病例、22例路易体痴呆（DLB）患者、1例特发性震颤患者以及20例年龄匹配的对照者。由于技术原因，未对嗅觉系统进行研究。在所有PD患者的脑中，延髓核、脑桥核、蓝斑和黑质均存在α-突触核蛋白阳性包涵体及神经元缺失，杏仁核（24%）、异皮质（58%）、扣带区（34%）和新皮质（26.5%）也有额外病变。所有PD病例均符合Braak等人（2003年，《神经生物学衰老》24:197）提出的病理分期4 - 6期。在大多数DLB病例中，α-突触核蛋白病理改变和神经退行性变的分布与PD病理分期的5期和6期相对应。特发性震颤患者及48.2%的AD病例未显示路易体病理改变；在其他AD患者的脑中，多个脑区可见α-突触核蛋白阳性包涵体。所有对照者均未显示路易体病理改变。在12例偶发性路易体病（无临床帕金森体征）病例中，7例在形态学上符合PD分期3或4期。在另外6例AD病例中，2例有帕金森症状，可见蓝斑、黑质、基底核和异皮质有明显损害，但延髓核保存。初步数据在很大程度上证实了Braak提出的脑病理分期，尽管部分临床诊断为PD的病例符合通常被认为是“临床前期”的3期。此外，一些未显示延髓核受累的病例在其他脑区出现广泛的类似PD的病理改变，提示偏离了所提出的确立的扩展模式，且偶发性路易体病理改变可能仅影响蓝斑和黑质。DLB和PD之间路易体病理改变的显著相似性表明这两种疾病之间存在密切的形态学关系。许多无帕金森症状的散发性AD病例中出现广泛的路易体病变，但发病机制及临床影响尚不清楚。AD与PD之间，尤其是与α-突触核蛋白阳性病变相关的关系有待进一步阐明[已校正]
