Mann D M
Department of Pathology, University of Manchester, Great Britain.
Ann Med. 1989;21(2):133-6. doi: 10.3109/07853898909149200.
In this paper, it is argued that the earliest morphological changes of Alzheimer's disease involve the formation of the senile plaque. Key molecular events in this process implicate a deposition of amyloid (A4) protein and an accumulation of an oligosaccharide. These 'preplaques' do not contain neurites, and may first appear in the hippocampus and amygdala, but later involving all association areas of cortex. They may be caused by a capillary defect leading to an altered blood-brain barrier function. The amyloid protein later increases, becomes arranged in a beta-pleated manner recognizable by thioflavin and at this stage plaques also usually contain paired helical filaments within neurites. Similar filaments also form the neurofibrillary tangles of affected perikarya, appearing initially within the large neurones of the entorhinal cortex, but later affecting neurones widely throughout the hippocampus, amygdala, cortex and subcortex. Tangle accumulation leads to impairment of neurone function, development of clinical dementia and ultimately, cell death. Progression of this process leads to extensive cortical plaque and also of those anatomically projecting to the affected cortex.
本文认为，阿尔茨海默病最早的形态学变化涉及老年斑的形成。这一过程中的关键分子事件包括淀粉样蛋白（A4）的沉积和低聚糖的积累。这些“前体斑块”不含神经突，可能首先出现在海马体和杏仁核，但随后会累及皮质的所有联合区域。它们可能是由毛细血管缺陷导致血脑屏障功能改变引起的。淀粉样蛋白随后增加，以硫黄素可识别的β折叠方式排列，在此阶段，斑块内的神经突通常也含有双螺旋丝。类似的细丝也形成受影响神经核周体中的神经原纤维缠结，最初出现在内嗅皮质的大神经元内，但随后广泛影响海马体、杏仁核、皮质和皮质下的神经元。缠结的积累导致神经元功能受损、临床痴呆的发展，并最终导致细胞死亡。这一过程的进展会导致广泛的皮质斑块以及那些向受影响皮质投射的解剖结构中的斑块。
