Lashley T, Holton J L, Verbeek M M, Rostagno A, Bojsen-Møller M, David G, van Horssen J, Braendgaard H, Plant G, Frangione B, Ghiso J, Revesz T
Queen Square Brain Bank, Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
Neuropathol Appl Neurobiol. 2006 Oct;32(5):492-504. doi: 10.1111/j.1365-2990.2006.00747.x.
Molecular chaperons or amyloid-associated proteins (AAPs) are deposited in vascular and parenchymal amyloid lesions in Alzheimer's disease (AD) and other amyloidoses. AAPs, such as apolipoprotein E (ApoE) or apolipoprotein J (ApoJ) have been strongly implicated in the pathogenesis of AD in vitro and in vivo. Furthermore the possession of the ApoE in4 allele is a well-studied risk factor for AD. In view of the similarities between AD and both familial British dementia (FBD) and familial Danish dementia (FDD), we investigated the presence of AAPs in these two diseases to understand better their role in the general process of amyloidogenesis. Immunohistochemistry for ApoE, ApoJ, serum amyloid P (SAP), alpha-1-antichymotrypsin, cystatin C, heparan sulphate proteoglycans, such as agrin, perlecan, syndecans, glypican-1 and for heparan sulphate glycosaminoglycan (HS GAG) side chains was carried out together with immunohistochemical preparations specific to the amyloid subunits. Significant or extensive staining for ApoE, ApoJ, agrin, glypican-1 and HS GAG side chains was found in both amyloid (fibrillar) and preamyloid (nonfibrillar) deposits in FBD and FDD. The remaining AAPs, including SAP, were predominantly found in amyloid lesions. Only very weak staining was present in a small proportion of the amyloid lesions using perlecan immunohistochemistry. These findings suggest that the deposition patterns of AAPs in FBD and FDD are mostly similar to those in AD. The presence of AAPs in the preamyloid lesions supports the notion that chaperon molecules may play a role in the early steps of fibrillogenesis.
分子伴侣或淀粉样蛋白相关蛋白（AAPs）沉积于阿尔茨海默病（AD）及其他淀粉样变性疾病的血管和实质淀粉样病变中。诸如载脂蛋白E（ApoE）或载脂蛋白J（ApoJ）等AAPs在体外和体内均与AD的发病机制密切相关。此外，载脂蛋白Eε4等位基因的存在是一个经过充分研究的AD风险因素。鉴于AD与家族性英国痴呆（FBD）和家族性丹麦痴呆（FDD）之间的相似性，我们研究了这两种疾病中AAPs的存在情况，以更好地了解它们在淀粉样蛋白生成的一般过程中的作用。我们进行了针对ApoE、ApoJ、血清淀粉样蛋白P（SAP）、α-1抗糜蛋白酶、胱抑素C、硫酸乙酰肝素蛋白聚糖（如集聚蛋白、基底膜聚糖、多配体蛋白聚糖、磷脂酰肌醇蛋白聚糖-1）以及硫酸乙酰肝素糖胺聚糖（HS GAG）侧链的免疫组织化学检测，同时还进行了针对淀粉样亚基的免疫组织化学检测。在FBD和FDD的淀粉样（纤维状）和淀粉样前体（非纤维状）沉积物中均发现了ApoE、ApoJ、集聚蛋白、磷脂酰肌醇蛋白聚糖-1和HS GAG侧链的显著或广泛染色。其余的AAPs，包括SAP，主要存在于淀粉样病变中。使用基底膜聚糖免疫组织化学检测时，仅在一小部分淀粉样病变中出现非常微弱的染色现象。这些发现表明，AAPs在FBD和FDD中的沉积模式大多与AD中的相似。淀粉样前体病变中AAPs的存在支持了分子伴侣可能在纤维形成早期步骤中发挥作用的观点。
