Lewy body-related α-synucleinopathy in the aged human brain
Lewy body-related α-synucleinopathy in the aged human brain
复制标题
DOI：
10.1007/s00702-004-0138-7
复制
发表时间：
2004-10-01
影响因子：
3.3
通讯作者：
Jellinger, KA
中科院分区：
文献类型：
--
作者：
Jellinger, KA
为明确路易体（LB）相关α -突触核蛋白病在衰老及各种神经退行性疾病中的意义，我们对260例老年患者的大脑进行了发病率和地形模式的检测，包括尸检证实的阿尔茨海默病（AD） 116例，临床及尸检证实的帕金森病（PD） 71例，伴路易体痴呆（DLB） 38例，进行性核上性麻痹（PSP） 8例，老年性震颤1例，还有26名年龄匹配的对照组，没有神经精神疾病。采用免疫组织化学对α -突触核蛋白（AS）阳性病变进行半定量评估。由于技术原因，嗅觉系统没有得到系统的研究。所有pd脑在髓核、桥脑核和中脑核均显示as阳性病变，累及基底核（90.1%）、边缘皮层（58.9%）、扣带皮层（46%）、杏仁核、CA /3海马区（36.2%）、新皮层（28.8%）和纹状体（11%）。根据Braak et al.(2003)， 88%的临床PD病例对应于LB病理4-6期，12%对应于3期。84%的DLB大脑为PD 5期或6期，17%为PD 4期，伴有和不伴有神经性AD病理的DLB之间无显著差异，提示这些疾病在形态上具有相似性。6/8的PSP和老年性震颤患者、49.1%的AD和69%的老年对照均为阴性。AD中as阳性病变发生率从中脑（24-28%）、边缘皮层和杏仁核（17-18%）、基底核和髓核（13-17%）、扣带皮层（12%）、CA 2/3区（8%）到新皮层（2%）依次下降，无性别差异，与AD病理严重程度无关（平均Braak期5.1）。AS阳性病变的AD患者，特别是杏仁核AS病理的AD患者，在死亡时比阴性患者更老（86.6岁对83.3岁），但这种差异没有统计学意义。15例AD（其中7例伴有轻度PD症状）和3例无帕金森症状但LB病理分期为3期的老年对照（n=5）和4例（n=13）被认为是“偶发性LB病”。16例无帕金森症状的AD大脑在不同区域均有AS阳性病变，但未累及髓质，提示偏离了所提出的刻板扩张模式。在无症状的老年对照中，有31%的人发现as病理位于中脑和边缘皮层。这些数据1。在很大程度上证实了Braak对PD患者lb病理的分期；2. 提示PD（脑干型）与DLB伴或不伴AD病理之间的形态学和致病关系；3. 约50%的阿尔茨海默病患者和约30%的老年对照者发生与lb相关的α -突触核蛋白病。然而，lb相关as病理的基本机制及其在老年脑和神经退行性疾病中的致病和临床意义有待进一步阐明。
To clarify the significance of Lewy body (LB)-related alpha-synucleinopathy in aging and various neurodegenerative disorders, its incidence and topographic pattern were examined in 260 brains of elderly patients, including 116 autopsy-proven cases of Alzheimer disease (AD), 71 cases of clinically and autopsy-proven Parkinson disease (PD), 38 of dementia with Lewy bodies (DLB), 8 patients with progressive supranuclear palsy (PSP), one with senile tremor, and 26 age-matched controls without neuropsychiatric disorders. Using immunohistochemistry, alpha-synuclein (AS) positive lesions were assessed semiquantitatively. For technical reasons, the olfactory system was not systematically studied. All PD-brains showed AS-positive lesions in medullary, pontine and mesencephalic nuclei, with involvement of the nucleus basalis (90.1%), limbic cortex (58.9%), cingulate cortex (46%), amygdala, CA 2/3 hippocampal region (36.2%), neocortex (28.8%), and striatum (11%). 88% of clinical PD cases corresponded to LB pathology stages 4-6, 12% to stage 3 according to Braak et al. (2003). 84% of DLB brains were PD stage 5 or 6 and 17% stage 4, without significant differences between DLB with and without neuritic AD pathology, suggesting morphologic similarities between these disorders. 6/8 PSP and senile tremor cases, 49.1% of AD and 69% of aged controls were negative. AS-positive lesions in AD showed decreasing incidence from midbrain (24-28%), limbic cortex and amygdala (17-18%), nucleus basalis and medullary nuclei (13-17%), cingulate cortex (12%), CA 2/3 region (8%) to neocortex (2%), without gender differences or relationship to the severity of AD pathology (mean Braak stage 5.1). AD cases with AS positive lesions, particularly those with AS pathology in the amygdala, were older at death than negative ones (86.6 vs 83.3 yrs), but this difference was not statistically significant. 15 AD cases (seven of them with mild PD symptoms) and 3 aged controls without parkinsonian signs but LB pathology stages 3 (n=5) and 4 (n=13) were considered "incidental LB disease". 16 AD brains without parkinsonian symptoms had AS positive lesions in various areas without medullary involvement, suggesting deviation from the proposed stereotypic expansion pattern. Located AS-pathology in the midbrain and limbic cortex was seen in 31% of asymptomatic aged controls. These data 1. largely confirm Braak's staging of LB-pathology in PD; 2. suggest morphologic and pathogenic relations between PD (brainstem type) and DLB with and without coexistent AD pathology; 3. the occurrence of LB-related alpha-synucleinopathy in about 50% of AD brains and about 30% of aged controls. However, the basic mechanisms of LB-related AS-pathology and their pathogenic and clinical relevance in aged brain and neurodegenerative disorders await further elucidation.