Li Q X, Whyte S, Tanner J E, Evin G, Beyreuther K, Masters C L
Department of Pathology, University of Melbourne, and Mental Health Research Institute of Victoria, Parkville, Australia.
Lab Invest. 1998 Apr;78(4):461-9.
Alzheimer's disease (AD) is characterized by the deposition of Abeta (betaA4) peptides of 39 to 43 amino acid residues, which are normal cellular metabolic products derived by proteolysis of the amyloid precursor protein (APP). The physiologic function of Abeta/APP in vivo is poorly understood. We analyzed human platelets for Abeta production by immunoprecipitation coupled to immunoblotting. A 4-kd Abeta fragment that comigrates with an Abeta40 synthetic peptide and reacts with several antibodies specific for the N- and C-termini of Abeta is detected. The majority of platelet Abeta appears to end at residue 40, as determined by immunoreactivity with an Abeta40-specific antibody. Furthermore, Abeta is secreted upon platelet stimulation with the physiologic agonists thrombin and collagen, together with secretion of soluble APP (sAPP). A comparison between serum and plasma shows a 1.6-fold increase in Abeta levels and a 2.4-fold increase in sAPP levels in serum. This is consistent with the view that platelets are the primary source of circulating Abeta and APP. The release of platelet Abeta by physiologic stimuli suggests that it may play a role in platelet aggregation and coagulation or in the repair mechanisms associated with injury.
阿尔茨海默病（AD）的特征是存在由39至43个氨基酸残基组成的β淀粉样蛋白（βA4）肽沉积，这些肽是淀粉样前体蛋白（APP）蛋白水解产生的正常细胞代谢产物。β淀粉样蛋白/APP在体内的生理功能尚不清楚。我们通过免疫沉淀结合免疫印迹分析了人血小板中β淀粉样蛋白的产生情况。检测到一个4kd的β淀粉样蛋白片段，它与β淀粉样蛋白40合成肽迁移率相同，并与几种针对β淀粉样蛋白N端和C端的特异性抗体发生反应。通过与β淀粉样蛋白40特异性抗体的免疫反应性测定，大多数血小板β淀粉样蛋白似乎在第40位残基处终止。此外，在用生理激动剂凝血酶和胶原蛋白刺激血小板时，β淀粉样蛋白会与可溶性APP（sAPP）一起分泌。血清和血浆的比较显示，血清中β淀粉样蛋白水平增加了1.6倍，sAPP水平增加了2.4倍。这与血小板是循环β淀粉样蛋白和APP的主要来源这一观点一致。生理刺激导致血小板β淀粉样蛋白释放表明，它可能在血小板聚集和凝血或与损伤相关的修复机制中发挥作用。
