Braak H, Braak E
Department of Anatomy, J.W. Goethe University, Frankfurt, Germany.
Neurobiol Aging. 1995 May-Jun;16(3):271-8; discussion 278-84. doi: 10.1016/0197-4580(95)00021-6.
Specific immunocytochemical methods (AT8) permit evaluation of neuronal changes well before the actual formation of neurofibrillary tangles and neuropil threads. Initial changes are found in the transentorhinal region (temporal lobe). From here the destructive process encroaches upon the entorhinal region, Ammon's horn, and neocortex. Initial changes occur in comparatively young individuals and can also be observed at the same predilection sites in a few species of old aged domestic animals. In a later state of destruction, AT8 immunoreactive neurons develop typical argyrophilic neurofibrillary tangles and neuropil threads. Six stages of disease propagation can be distinguished with respect to the location of the tangle-bearing neurons and the severity of changes (transentorhinal stages I-II: clinically silent cases; limbic stages III-IV: incipient Alzheimer's disease; neocortical stages V-VI: fully developed Alzheimer's disease). Whole mount techniques reveal the lesional pattern of the particularly severely involved superficial entorhinal layer as seen from the free surface of the parahippocampal gyrus. This approach facilitates recognition of even subtle pathologic changes throughout the entire extent of cortical territories such as the transentorhinal and entorhinal regions.
特定的免疫细胞化学方法（AT8）能够在神经原纤维缠结和神经毡丝实际形成之前很久就对神经元变化进行评估。最初的变化出现在内嗅皮质过渡区（颞叶）。从这里开始，破坏过程会侵袭内嗅区、海马角和新皮质。最初的变化出现在相对年轻的个体中，并且在一些老年家畜的相同偏好部位也能观察到。在破坏的后期，AT8免疫反应性神经元会形成典型的嗜银性神经原纤维缠结和神经毡丝。根据含缠结神经元的位置和变化的严重程度，可以区分出疾病传播的六个阶段（内嗅皮质过渡区I-II期：临床无症状病例；边缘系统III-IV期：早期阿尔茨海默病；新皮质V-VI期：完全发展的阿尔茨海默病）。整装技术揭示了从海马旁回自由表面观察到的特别严重受累的浅层内嗅皮质层的病变模式。这种方法有助于识别整个皮质区域，如内嗅皮质过渡区和内嗅区，甚至细微的病理变化。
