Tau and α-synuclein brainstem pathology in Alzheimer disease:: relation with extrapyramidal signs
Tau and α-synuclein brainstem pathology in Alzheimer disease:: relation with extrapyramidal signs
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DOI：
10.1007/s00401-006-0146-9
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发表时间：
2007-01-01
影响因子：
12.7
通讯作者：
Jellinger, Kurt A.
中科院分区：
文献类型：
--
作者：
Attems, Johannes;Quass, Magdalena;Jellinger, Kurt A.
阿尔茨海默病（AD）的锥体外系症状（EPS）往往随着疾病的严重程度而增加。他们的神经病理学基础是一个讨论的问题。我们研究了伴有和不伴有EPS的AD患者脑干中的tau和α-突触核蛋白（AS）病理。在160例尸检证实的AD老年受试者（110例女性，50例男性，年龄61-102岁，平均84.1 ± 8.3 SD岁）中，151例（94.4%）为痴呆，35例（21.9%）有临床报告的EPS（僵硬、运动迟缓、步态障碍）。神经病理学检查包括根据现行标准对AD进行标准化分类，并半定量评估黑质（SN）、蓝斑（LC）中的神经元丢失，脑干中的tau和AS病变，以及脑血管病变。在Braak分期较高的患者中，EPS的患病率仅略高。脑干中的Tau病理随着Braak分期的增加而显著增加，而AS病变则没有。EPS与黑质细胞丢失的相关性最好（P < 0.001），而与除延髓（P <0.001）外的其他脑区AS病理变化的相关性较低（P <0.05）。虽然黑质的两种病理与神经元丢失相关（P < 0.001），但黑质tau病变（88.5%的EPS阳性病例中存在）（55.6%的EPS阳性病例中无AS病变）与EPS无关。在完全发展的AD中，额外的脑血管变化显然不影响EPS症状的发展。与其他最近的数据，这些结果表明，SN中的神经元损失，部分相关的tau病变，是一个主要的病理基质的EPS在AD，但一些情况下，与和没有EPS可能显示没有或只有最小的黑质变化。然而，老年患者的EPS通常与黑质tau病变和较高的Braak分期相关，可能是重度神经炎性AD病理学的替代标志物。
Extrapyramidal symptoms (EPS) in Alzheimer disease (AD) often increase with disease severity. Their neuropathological substrate is a matter of discussion. We investigated tau and alpha-synuclein (AS) pathologies in brainstem in AD patients with and without EPS. Among 160 elderly subjects with autopsy-proven AD (110 female, 50 male, aged 61-102, mean 84.1 +/- 8.3 SD years), 151 (94.4%) being demented, 35 (21.9%) had clinically reported EPS (rigidity, bradykinesia, gait impairment). Neuropathological examination included standardized classification of AD according to current criteria, and semiquantitative assessment of neuronal loss in substantia nigra (SN), locus coeruleus (LC), and of tau and AS lesions in brainstem, and, in addition, of cerebrovascular lesions. The prevalence of EPS was only slightly more frequent in higher Braak stages. Tau pathology in brainstem significantly increased with increasing Braak stages, while AS lesions did not. EPS correlated best with SN cell loss (P < 0.001) and much less with AS pathology in several brain areas (P < 0.05), except in medulla oblongata (P < 0.001). Although both pathologies in substantia nigra correlated with neuron loss (P < 0.001), nigral tau lesions, present in 88.5% of EPS positive cases (without AS lesions in 55.6%), did not correlate with EPS. Additional cerebrovascular changes apparently did not influence the development of EPS symptoms in fully developed AD. With other recent data, these results suggest that neuronal loss in SN, partly related to tau lesions, is a major pathological substrate of EPS in AD, but some cases with and without EPS may show no or only minimal nigral changes. However, often associated with nigral tau lesions and higher Braak stages, EPS in elderly patients may be a surrogate marker for severe neuritic AD pathology.