Takeda A, Mallory M, Sundsmo M, Honer W, Hansen L, Masliah E
Department of Neurosciences, University of California, San Diego, School of Medicine La Jolla, 92093-0624, USA.
Am J Pathol. 1998 Feb;152(2):367-72.
The precursor of the non-Abeta component of Alzheimer's disease amyloid (NACP) (also known as a-synuclein) is a presynaptic terminal molecule that accumulates in the plaques of Alzheimer's disease. Recent studies have shown that a mutation in NACP is associated with familial Parkinson's disease, and that Lewy bodies are immunoreactive with antibodies against this molecule. To clarify the patterns of accumulation and differences in abnormal compartmentalization, we studied NACP immunoreactivity using double immunolabeling and laser scanning confocal microscopy in the cortex of patients with various neurodegenerative disorders. In Lewy body variant of Alzheimer's disease, diffuse Lewy body disease, and Parkinson's disease, NACP was found to immunolabel cortical Lewy bodies, abnormal neurites, and dystrophic neurites in the plaques. Double-labeling studies showed that all three of these neuropathological structures also contained ubiquitin, synaptophysin, and neurofilament (but not tau) immunoreactivity. In contrast, neurofibrillary tangles, neuropil threads, Pick bodies, ballooned neurons, and glial tangles (most of which were tau positive) were NACP negative. These results support the view that NACP specifically accumulates in diseases related to Lewy bodies such as Lewy body variant of Alzheimer's disease, diffuse Lewy body disease, and Parkinson's disease and suggests a role for this synaptic protein in the pathogenesis of neurodegeneration.
阿尔茨海默病淀粉样蛋白非Aβ成分（NACP）（也称为α-突触核蛋白）的前体是一种突触前终末分子，在阿尔茨海默病的斑块中积聚。最近的研究表明，NACP的突变与家族性帕金森病有关，并且路易小体与针对该分子的抗体发生免疫反应。为了阐明积聚模式和异常分隔的差异，我们使用双重免疫标记和激光扫描共聚焦显微镜研究了各种神经退行性疾病患者皮质中的NACP免疫反应性。在阿尔茨海默病路易小体变异型、弥漫性路易小体病和帕金森病中，发现NACP免疫标记皮质路易小体、异常神经突和斑块中的营养不良性神经突。双重标记研究表明，所有这三种神经病理结构也含有泛素、突触素和神经丝（但不包括tau）免疫反应性。相比之下，神经原纤维缠结、神经毡丝、Pick小体、气球样神经元和胶质缠结（其中大多数为tau阳性）NACP呈阴性。这些结果支持这样一种观点，即NACP特异性地积聚在与路易小体相关的疾病中，如阿尔茨海默病路易小体变异型、弥漫性路易小体病和帕金森病，并提示这种突触蛋白在神经退行性变的发病机制中起作用。
