摘要
与阿尔茨海默病 (Alzheimerdisease ,AD)痴呆的严重性最有关的和最合理的原因是触突丧失。尽管 β 淀粉样蛋白假说盛行 ,但它引起突触丧失是微弱的 ;其他的病理变化更能说明突触损伤现象。轴突终末的正常依赖于轴浆流 ;轴浆流的功能需要完整无损的微管和运动蛋白———驱动蛋白、动力蛋白和发动蛋白。从早期AD的电镜研究以来 ,就已知在AD神经元中微管数量减少。正常情况下 ,微管与未聚合的微管蛋白是平衡的 ;稳定的形成成分依赖于tau与微管的正常结合。但在AD中 ,tau的过磷酸化导致缠结形成和微管溃解。缠结的数量并不足以说明皮层神经元和突触的丧失 ;但在聚合前的缠结状态中 ,tau的过磷酸化无疑起重要作用。
The strongest physical correlate wi th the severity of dementia in Alzheimer's disease and its most rational cause are the loss of neocortical and hoppocampal synapses .Evidence, showing that β amyloid causes that loss is weak despite the popularity of that hypothesis. Ot her changes can better explain that damaging phenomenon. Axonal terminals are de pendent on axoplasmic flow,and that function requires intact microtubules and th e motor proteins kinesin,dynein and dynamin.It has been known since the earliest electron microscopic studies of AD that neuronal microtubules are lessened in n umber. Tubules are normally in equilibrium with unpolymerized tubulin,and the st ability of the formed elements is dependent on normal binding of tau to the tubu le. But ,as is well known ,tau is abnormally hyperphosphorylated in AD leading t o tangle formation and to dissolution of the tubules.Tangles are insufficient in number to account for the cortical loss of neurons and synapses, but hyperphosp horylated tau in the unpolymerized pre tangle state undoubtedly plays a role.Ab normalities in the motor proteins are now being investigated and these would con tribute to the loss of synapses in AD by way diminished axoplasnic flow.
