Braak H, Braak E
Department of Anatomy, J.W. Goethe University, Frankfurt/Main, Federal Republic of Germany.
J Neural Transm Suppl. 1998;53:127-40. doi: 10.1007/978-3-7091-6467-9_11.
Alzheimer's disease entails multiple neuronal systems and results from neuronal cytoskeletal degeneration of only a few types of nerve cells. Essential for neuropathological diagnosis is assessment of the presence of neurofibrillary tangles and neuropil threads. The destructive process begins in predisposed cortical induction sites, thereafter invading other portions of the cerebral cortex and specific sets of subcortical nuclei in a predictable sequence with little variation. The location of the tangle-bearing neurons and severity of the pathology allow the distinction of six stages in disease propagation (transentorhinal I-II: clinically silent cases; limbic III-IV: incipient Alzheimer's disease; neocortical V-VI: fully-developed Alzheimer's disease). The pattern of appearance of the neurofibrillary changes bears a striking resemblance to the inverse sequence of cortical myelination. The average myelin content is a negative image of the density of intraneuronal lipofuscin deposits. Pigment-laden neurons endowed with a long, thin, and sparsely myelinated axon are prone to develop AD-related changes. The emergence of the first neurofibrillary changes, at whatever age these occur, signals the onset of a degenerative process that persists until death. An extended period of time elapses between the beginning of histologically verifiable lesions and the appearance of initial clinical symptoms. Once initiated, however, cytoskeletal deterioration inexorably progresses, and neither remission nor recovery is observed.
阿尔茨海默病涉及多个神经元系统，是由少数几种神经细胞的神经元细胞骨架退化引起的。神经病理学诊断的关键是评估神经原纤维缠结和神经毡线的存在。破坏过程始于易感的皮质诱导部位，此后以可预测的顺序侵入大脑皮质的其他部分和特定的皮质下核组，变化很小。含有缠结的神经元的位置和病理严重程度有助于区分疾病进展的六个阶段（跨内嗅区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）。神经原纤维变化的出现模式与皮质髓鞘形成的逆序惊人地相似。平均髓鞘含量是神经元内脂褐素沉积密度的负像。具有长、细且髓鞘稀疏的轴突的色素沉着神经元容易发生与AD相关的变化。无论在什么年龄出现首次神经原纤维变化，都标志着一个持续到死亡的退化过程的开始。从组织学上可证实的病变开始到最初临床症状出现之间会经过一段很长的时间。然而，一旦开始，细胞骨架的恶化就会不可阻挡地进展，不会出现缓解或恢复。
