Wang D, Munoz D G
Department of Pathology, University of Western Ontario, London, Canada.
J Neuropathol Exp Neurol. 1995 Jul;54(4):548-56. doi: 10.1097/00005072-199507000-00009.
We have investigated the relationship of plaque dystrophic neurites expressing beta-amyloid precursor protein (beta APP) to those bearing markers of neurofibrillary degeneration (tau), or accumulating the synaptic protein chromogranin A (CgA). In cortical and hippocampal plaques in Alzheimer's disease (AD) beta APP colocalized with CgA in a neuritic population largely distinct from the subset of neurites labeled by tau. Putaminal plaques generally incorporated only CgA/beta APP, but not tau neurites, and with a rare exception cerebellar plaques were not associated with neurites. Neocortical and hippocampal plaques, the only common type in a group of elderly non-demented subjects (non-AD), incorporated CgA/beta APP, but not tau neurites. In addition to this qualitative difference between the two groups, neocortical plaques with CgA/beta APP neurites were one order of magnitude more common in AD than in non-AD. We propose a hierarchical model of plaque formation in which A beta deposits do not incorporate tau neurites unless neurites bearing synaptic proteins and beta APP are also present. Finally, the minimal association of tau neurites with putaminal plaques, in the presence of tau-immunoreactive neuropil threads and neurofibrillary tangles in the neighborhood, suggests that plaque-independent mechanisms of development of tau neurites operate in AD.
我们研究了表达β-淀粉样前体蛋白（βAPP）的斑块营养不良性神经突与那些带有神经原纤维变性标志物（tau）或积累突触蛋白嗜铬粒蛋白A（CgA）的神经突之间的关系。在阿尔茨海默病（AD）的皮质和海马斑块中，βAPP与CgA在很大程度上与由tau标记的神经突亚群不同的神经突群体中共定位。壳核斑块通常仅包含CgA/βAPP，而不包含tau神经突，并且除了极少数例外，小脑斑块与神经突无关。新皮质和海马斑块是一组老年非痴呆受试者（非AD）中唯一常见的类型，包含CgA/βAPP，但不包含tau神经突。除了两组之间的这种质的差异外，带有CgA/βAPP神经突的新皮质斑块在AD中比在非AD中常见一个数量级。我们提出了一个斑块形成的层次模型，其中β淀粉样蛋白沉积物不会包含tau神经突，除非同时存在带有突触蛋白和βAPP的神经突。最后，在附近存在tau免疫反应性神经毡丝和神经原纤维缠结的情况下，tau神经突与壳核斑块的最小关联表明，tau神经突的斑块非依赖性发育机制在AD中起作用。
