Wolozin B, Maheshwari S, Jones C, Dukoff R, Wallace W, Racchi M, Nagula S, Shulman N R, Sunderland T, Bush A
Section on Geriatric Psychiatry, NIMH, Bethesda, MD 20892, USA.
Mol Psychiatry. 1998 Nov;3(6):500-7. doi: 10.1038/sj.mp.4000451.
The beta-amyloid (A beta) peptide is present both in serum and in platelets, however it is unclear whether A beta plays a role in platelet function. We have now investigated the effects of soluble A beta on platelet function and have found that low levels (0.1-1 nM) of soluble A beta augment ADP-dependent platelet aggregation and translocation of focal adhesion kinase to the platelet cytoskeleton. Addition of A beta to gel-filtered platelets along with concentrations of adenosine diphosphate (ADP) producing submaximal aggregation responses increased the aggregation response by over 2-fold depending on the ADP:A beta ratios. The structure activity requirements for A beta activity showed intriguing constraints. Only full length A beta has significant activity. Truncated A beta peptides, such as A beta(1-16) or A beta(25-35), or reverse A beta(40-1) all show little or no activity. We also examined the activity of mutant A beta peptides, corresponding with the APP(692A-G) and APP(693E-Q) (at A beta21 and A beta22, respectively) which are found in familial Alzheimer's disease and hereditary cerebral hemorrhagic amyloidosis, Dutch type (HCHWA-D), and found that these peptides showed little or no activity. These results suggest that A beta interacts with platelets in a highly specific manner and may play a role in regulating platelet function.
β-淀粉样蛋白（Aβ）肽在血清和血小板中均有存在，但尚不清楚Aβ是否在血小板功能中发挥作用。我们现在研究了可溶性Aβ对血小板功能的影响，发现低水平（0.1 - 1 nM）的可溶性Aβ可增强ADP依赖性血小板聚集以及粘着斑激酶向血小板细胞骨架的转位。将Aβ添加到凝胶过滤的血小板中，同时加入产生次最大聚集反应浓度的二磷酸腺苷（ADP），根据ADP与Aβ的比例，聚集反应可增加2倍以上。Aβ活性的结构活性要求显示出有趣的限制。只有全长Aβ具有显著活性。截短的Aβ肽，如Aβ（1 - 16）或Aβ（25 - 35），或反向的Aβ（40 - 1）均显示出很少或没有活性。我们还检测了与家族性阿尔茨海默病和荷兰型遗传性脑出血性淀粉样变性（HCHWA - D）中发现的APP（692A - G）和APP（693E - Q）（分别位于Aβ21和Aβ22）相对应的突变Aβ肽的活性，发现这些肽显示出很少或没有活性。这些结果表明，Aβ以高度特异性的方式与血小板相互作用，可能在调节血小板功能中发挥作用。
