Chen M, Inestrosa N C, Ross G S, Fernandez H L
Neuroscience Research Laboratory, Department of Veterans Affairs Medical Center, Bay Pines, Florida 33504, USA.
Biochem Biophys Res Commun. 1995 Aug 4;213(1):96-103. doi: 10.1006/bbrc.1995.2103.
The main component of Alzheimer's disease (AD) amyloid deposits is amyloid beta-peptide (A beta), a fragment of the larger amyloid precursor protein (APP). The cellular source of A beta is not known, but a circulatory origin has been postulated. We studied human blood from healthy individuals and found that platelets account for almost 90% of the total anti-A beta immunoreactivity detected in whole blood. Using reverse-phase HPLC, we identified a platelet peptide which corresponds to A beta by three criteria: (a) it shares a retention time with the synthetic A beta 1-40 peptide in two consecutive HPLC tests; (b) it interacts with two anti-A beta antibodies in separate ELISAs; and, (c) its partial N-terminal amino acid sequence closely matches that of A beta. The detection of this peptide in platelets indicates that, aside from the well-known non-amyloidogenic (secretory) pathway, the processing of APP in platelets from healthy individuals also involves an amyloidogenic pathway. These findings are consistent with the view that platelets are one of the major sources of A beta in the circulation.
阿尔茨海默病（AD）淀粉样沉积物的主要成分是β-淀粉样肽（Aβ），它是较大的淀粉样前体蛋白（APP）的一个片段。Aβ的细胞来源尚不清楚，但有人推测其来源于循环系统。我们研究了健康个体的血液，发现血小板几乎占全血中检测到的总抗Aβ免疫反应性的90%。利用反相高效液相色谱法，我们通过三个标准鉴定出一种与Aβ相对应的血小板肽：（a）在连续两次高效液相色谱测试中，它与合成的Aβ1-40肽具有相同的保留时间；（b）在单独的酶联免疫吸附测定中，它与两种抗Aβ抗体相互作用；以及（c）其部分N端氨基酸序列与Aβ的序列高度匹配。在血小板中检测到这种肽表明，除了众所周知的非淀粉样生成（分泌）途径外，健康个体血小板中APP的加工还涉及淀粉样生成途径。这些发现与血小板是循环中Aβ的主要来源之一这一观点一致。
