摘要目的 探讨老龄脑组织神经变性疾病相关蛋白质异常沉积与脑功能障碍间的关系.方法 对2005年1月至2006年12月解放军总医院尸检老龄脑组织进行beta-amyloid(Aβ)、tau、α-synuclein和泛素免疫组织化学染色,采用the Consortium to Establish a Registry for Alzheimer's Disease (CREAD)方法半定量观察Aβ阳性核心斑,Braak方法对tau阳性神经原纤维缠结(NFT)和α-synuclein阳性路易小体进行分级,分析其与认知功能及运动功能障碍之间的关系.结果 该院连续尸检的年龄在78至95岁16例脑组织中,发现Aβ阳性核心斑13例,相当于CREAD稀少2例、中度2例、重度9例.Aβ阳性脑淀粉样血管变性8例,其中轻度6例,中、重度2例;tau阳性NFT 12例,其中Braak分期Ⅰ～Ⅱ期6例、Ⅲ～Ⅳ期4例、Ⅴ～Ⅵ期2例;CREAD重度Aβ阳性核心斑,同时并存新皮质大量tau/泛素阳性神经炎斑以及tau阳性NFT Braak分期Ⅳ期以上的5例病例,临床均存在认知功能障碍;另外4例CREAD重度Aβ阳性核心斑病例中,1例合并脑干α-synuclein阳性路易小体,临床存在中度认知功能障碍,其余3例均未出现认知功能障碍;α-synuclein阳性路易小体病4例,临床上均存在不同程度帕金森样运动功能障碍症状;泛素阳性结构13例,见于神经炎斑、NFT、路易小体等结构.结论 Aβ蛋白沉积是正常脑老化及认知功能障碍患者的脑组织重要标志性蛋白之一;CREAD重度Aβ阳性核心斑同时并存BraakⅣ期以上tau阳性NFT与阿尔茨海默病认知功能障碍密切相关;脑干大量α-synuclein阳性路易小体提示患者临床上可能存在帕金森样运动障碍症状;老龄脑组织常见泛素阳性表达,但缺乏疾病特异性.

abstractsObjective To recognize relationship of protein related neurodegeneration abnormal aggregation in the aged brains with their cognitive and motor functions.Methods Brain tissues from the consecutive autopsy cases of the aged from January 2005 to December 2006 in PLA General Hospital were carried out for immunohistochemical staining with beta amyloid,tau,α-synuclein and ubiquitin antibodies.The consortium to establish a registry for Alzheimer' s disease (CERAD) was used to semi-quantitatively analyze Aβ positive core plaques density and Braak staging for tau positive neurofibrillary tangles (NFTs)and α-synuclein positive Lewy bodies.In addition,Aβ positive cerebral amyloid angiopathy (CAA),neuritic plaques and various ubiquitin positive structures were also observed.The relationship of these protein abnormal depositions in the aged brains with cognitive and motor functions were analyzed.Results In brain tissues of 16 consecutive autopsy cases of the aged from 78 to 95 years,there were 13 cases with Aβ positive core plaques,their density was 2 cases with sparse,2 cases with moderate and 9 cases with frequent,respectively,according to CREAD.Eight cases with Aβ positive CAA were found,including 6 cases of mild CAA and 2 cases of severe CAA.There were 12 cases with tau positive NFTs,including 6 cases with Braak stage Ⅰ-Ⅱ,4 cases with stage Ⅲ-Ⅳ and 2 cases with stageⅤ-Ⅵ.There were 5 cases with frequent Aβ core plaques,meanwhile existing numerous tau/ubiquitin positive neuritic plaques and Braak stage Ⅳ-Ⅵ of tau positive NFTs,all of them presented cognitive dysfunction.Among 4 other cases with frequent Aβ core plaques,only one case coexisted α-synuclein positive Lewy bodies showed moderate cognitive impairment,remaining 3 cases did not present cognitive dysfunction.There were 4 cases with α-synuclein positive Lewy bodies in the brainstem,and all of these cases presented parkinsonian motor dysfunction.13 cases with ubiquitin positive structures were found.Conclusions Beta amyloid protein positive deposit in the aged brain is an important marker of normal brain aging and cognitive impairment;frequent Aβ core plaques in the neocortex plus Braak Ⅳ and above tau positive NFTs are closely related to cognitive dysfunction of Alzheimer's disease; α-synuclein positive Lewy bodies in the brainstem is one of the important pathological markers of parkinsonian motor disorders; ubiquitin deposition involves the development of some characteristic structures of several neurodegenerative diseases.