路易体相关病理改变在捐献人脑组织中的分布及与生前认知关系研究

发布时间：2018-07-09 10:46

本文选题：路易体病 + 帕金森病　；参考：《北京协和医学院》2017年博士论文

【摘要】：研究背景路易体病(Lewy body disease,LBD)是一种常见的神经退行性疾病,以路易小体(Lewy body,LB)在神经元胞体和轴突内的沉积为主要病理表现。帕金森病(Parkinson disease,PD)是最常见的LBD,病理表现为黑质神经元的丢失以及以α-synuclein为主要成分的LB沉积。该病临床早期以静止性震颤、运动迟缓等运动系统表现为主,晚期可出现认知障碍等非运动系统症状。ApoE ε4以及合并AD病理改变可能与PD出现认知损伤相关。在国内尚缺乏基于人脑组织库的对PD以及PD认知损害的临床病理研究。研究目的本研究旨在探究路易体相关病理改变(Lewy-related pathology,LRP)在中国捐献人脑组织中的分布情况,进一步探究PD及PD相关认知损伤的临床病理联系。研究方法本研究共纳入中国医学科学院北京协和医学院人脑组织库中76例具有临床信息、ECog认知评分、ABC评分的捐献者人脑组织,进一步进行α-synuclein染色以及ApoE基因分型。针对α-synuclein染色阳性的病例,按照Braak LRP分期标准对染色结果进行分期,并利用描述统计以及秩和检验分析PD和PD认知损害的临床病理关系。研究结果在本研究中,根据捐献者家属提供的临床病史,PD诊断敏感度为66.7%,特异度为98.6%;假阳性率为33.3%,假阴性率为1.4%。LB分期可能与临床认知损害相关。随着Braak分期的升高,ECog总分及ECog各项评分呈上升趋势(ECog总分:p = 0.091;记忆力:p = 0.079;语言:p= 0.068;视空间:p = 0.060;计划:p=0.255;组织:= 0.064;注意力:= 0.129)。PD患者伴认知损伤较为常见,LB合并AD病理改变可能共同促进认知损害,且ApoE ε4携带者可能更容易发生认知损伤。研究结论根据目前的临床诊断标准,对PD及PD认知损伤的认识可能存在不足。PD认知损伤可能与LB合并AD病理改变相关,且ApoE ε4携带者可能更加具有认知损伤的易感性。
[Abstract]:Background Lewy body disease (LBD) is a common neurodegenerative disease characterized by the deposition of Lewy body LB in neuronal bodies and axons. Parkinson disease (PD) is the most common type of LBD.It is characterized by the loss of neurons in the substantia nigra and the LB deposition of 伪 -synuclein. The early clinical manifestations of the disease were quiescent tremor, motor retardation and other motor system manifestations. The non-motor system symptoms such as cognitive impairment. ApoE 蔚 4 and the pathological changes associated with AD may be associated with cognitive impairment in PD. There is a lack of clinical and pathological studies on PD and PD cognitive impairment based on human brain tissue bank in China. Objective to investigate the distribution of Lewy-related pathological changes (LRP) in Chinese human brain and to explore the clinicopathological relationship between PD and PD related cognitive impairment. Methods 76 donors with clinical information ECog cognitive score and ABC score were included in the human brain tissue bank of Peking Union Medical College, Chinese Academy of Medical Sciences, and further 伪 -synuclein staining and ApoE genotyping were performed. The results of 伪 -synuclein staining were classified according to Braak LRP staging criteria, and the clinicopathological relationship between PD and PD cognitive impairment was analyzed by descriptive statistics and rank sum test. Results in this study, the sensitivity, specificity, false positive rate and false negative rate of PD diagnosis were 66.7 and 98.6, respectively, and the false negative rate of 1.4g / LB stage might be related to clinical cognitive impairment in this study, according to the clinical history provided by donor's family, the sensitivity of PD was 66.7, the specificity was 98.6, the false positive rate was 33.3 and the false negative rate was 1.4. With the increase of Braak stage, the total score of ECog and the scores of ECog showed an upward trend (ECog total score:% p = 0.091; memory: P = 0.079; language: p = 0.068; Visual space: p = 0.060; Planning: p0.255; organizational: 0.064; attention: 0.129) .PD patients with cognitive impairment are more common with LB combination. The pathological changes of AD may contribute to cognitive impairment, Moreover, ApoE 蔚 4 carriers may be more prone to cognitive impairment. Conclusion according to the current clinical diagnostic criteria, PD and PD cognitive impairment may be deficient. PD cognitive impairment may be associated with LB with AD pathological changes, and ApoE 蔚 4 carriers may be more susceptible to cognitive impairment.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R742.5

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