Duyckaerts C, Delaère P, He Y, Seilhean D, Hauw J J
Laboratoire de Neuropathologie R. Escourolle, Hôpital de la Salpêtrière, Paris.
Presse Med. 1994 May 14;23(18):848-54.
Deposition of large quantities of amyloid substance in the walls of the cerebral vessels and in the core of the senile plaques is characteristic of Alzheimer's disease. beta A4 peptide, the main component of the amyloid substance, is a product of a larger amyloid precursor protein which has the structure of a transmembrane receptor and is widely distributed throughout the body. The pathway leading to beta A4 is not yet fully established but could involve lysosomal degradation. It has been suggested that the beta A4 peptide is of neuronal or vascular origin. The beta A4 peptide is found in diffuse deposits in the cortex and cerebellum as well as in the basal ganglia before the classic senile plaques appear, mainly in layer III of the cerebral cortex. These diffuse deposits are devoid of degenerating neurites (i.e. containing abnormally phosphorylated tau protein). The classical senile plaques contain numerous degenerating neurites linking them to the connective network of the cortex. The intellectual deficit is correlated significantly to the density of the classical senile plaques but not to the density of the diffuse deposits. Although a mutation of the gene coding for the beta A4 peptide appears to be sufficient to induce (or accelerate) Alzheimer's disease, this is undoubtedly an exceptional mechanism. Certain mutations involving the beta A4 precursor protein gene increase in vitro the production of beta A4. The molecular and morphological steps leading, from the accumulation of the peptide (which in itself has no clinical expression) to the neurofibrillary pathology of the senile plaques and of the neurones (which are strongly correlated with clinical dementia), remain hypothetical.
在脑血管壁和老年斑核心中大量淀粉样物质的沉积是阿尔茨海默病的特征。β - A4肽是淀粉样物质的主要成分，是一种较大的淀粉样前体蛋白的产物，该蛋白具有跨膜受体结构，广泛分布于全身。导致β - A4产生的途径尚未完全明确，但可能涉及溶酶体降解。有人提出β - A4肽起源于神经元或血管。在经典老年斑出现之前，β - A4肽存在于皮质、小脑以及基底神经节的弥漫性沉积物中，主要在大脑皮质的第三层。这些弥漫性沉积物缺乏退化的神经突（即含有异常磷酸化的tau蛋白）。经典的老年斑含有大量退化的神经突，将它们与皮质的结缔组织网络相连。智力缺陷与经典老年斑的密度显著相关，但与弥漫性沉积物的密度无关。虽然编码β - A4肽的基因突变似乎足以诱发（或加速）阿尔茨海默病，但这无疑是一种特殊机制。某些涉及β - A4前体蛋白基因的突变在体外会增加β - A4的产生。从肽的积累（其本身没有临床症状）到老年斑和神经元的神经原纤维病理变化（与临床痴呆密切相关）的分子和形态学步骤仍然是假设性的。
