Progressive decrease of amyloid precursor protein carboxy terminal fragments (APP-CTFs), associated with tau pathology stages, in Alzheimer's disease
Progressive decrease of amyloid precursor protein carboxy terminal fragments (APP-CTFs), associated with tau pathology stages, in Alzheimer's disease
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DOI：
10.1046/j.1471-4159.2002.00901.x
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发表时间：
2002-05-01
影响因子：
4.7
通讯作者：
Delacourte, A
中科院分区：
文献类型：
--
作者：
Sergeant, N;David, JP;Delacourte, A
淀粉样前体蛋白（APP）功能障碍是阿尔茨海默病（AD）的一个重要病因。这种跨膜蛋白的加工在β-淀粉样肽（Abeta）产生的上游产生羧基末端片段（CTF）。APP-CTF的生理学意义仍然知之甚少，以及在家族性和非家族性AD（非FAD）中可能将APP功能障碍和tau病理学联系起来的关系。在本研究中，我们已经调查了定量和定性的变化，APP-CTFs在不同的大脑区域的非痴呆和痴呆患者的前瞻性和多学科研究。观察到五种APP-CTF的显著减少，这与tau病理学的进展密切相关，在大多数临床下AD和家族性或非FAD的AD病例中。此外，溶解度特性和之间的比例的五个频带也修改，无论是在Triton可溶性和/或不溶性馏分。总之，我们在这里首次展示了在Abeta产物上游的APP-CTF上直接观察到的修饰及其与tau病理学的关系，这可以反映AD的基本病因学机制。
Amyloid precursor protein (APP) dysfunction is a key aetiologic agent in Alzheimer's disease (AD). The processing of this transmembrane protein generates carboxy terminal fragments (CTFs) upstream of beta-amyloid peptide (Abeta) production. The physiologic significance of APP-CTFs is still poorly understood, as well as the relationship that could link APP dysfunction and tau pathology in familial and non-familial AD (non-FAD). In the present study, we have investigated the quantitative and qualitative changes of APP-CTFs in different brain areas of non-demented and demented patients from a prospective and multidisciplinary study. A significant decrease of the five APP-CTFs was observed, which correlated well with the progression of tau pathology, in most cases with infraclinical AD and AD, either familial or non-FAD. Furthermore, solubility properties and the ratio between the five bands were also modified, both in the Triton-soluble and/or -insoluble fractions. Together, we show here for the first time a modification directly observed on APP-CTFs upstream of Abeta products and its relationship with tau pathology, which could reflect the basic aetiological mechanisms of AD.