Amyloid β 1 – 42 deposits do not lead to Alzheimer ’ s neuritic plaques in aged dogs
Amyloid β 1 – 42 deposits do not lead to Alzheimer ’ s neuritic plaques in aged dogs
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淀粉样蛋白 β 1 – 42 沉积物不会导致老年犬出现阿尔茨海默氏症神经炎斑块
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发表时间：
1996
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影响因子：
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通讯作者：
B. Frangione
中科院分区：
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作者：
T. Wisniewski;M. Lalowski;M. Bobik;M. Russell;J. Strosznajder;B. Frangione
阿尔茨海默病(AD)是一种神经病理学疾病，以老年斑、嗜中性血管病变和神经原纤维缠结的形式沉积淀粉样蛋白(综述见文献[1])。老年性斑块和先天性血管病变的主要成分是一种39-44个氨基酸残基的多肽--淀粉样蛋白β(Aβ)[2-8]。在低浓度下，β被发现是生物体液的正常成分，它被称为Saβ(Saβ)[9-12]。SAβ主要是Aβ1-40，尽管存在更短和更长的序列，包括Aβ1-28和Aβ1-42[13]。神经性斑块淀粉样蛋白在1985年首次被测序[3]，并被发现主要延伸到Aβ42}43，而血管淀粉样蛋白最初被报道延伸到Aβ1-28[2]，后来延伸到Aβ39}40[5，14]。AβC末端的这种异质性归因于局部组织加工的差异。最近使用不同技术的报告也在血管淀粉样蛋白沉积中发现了Aβ42[15]。在两种类型的淀粉样沉积中，β都具有主要的β-Sheet结构；另一方面，Sa-β可能更多地是随机卷曲的，或α-螺旋的。老年斑形成的早期阶段是“前叶样斑”或弥漫性斑块[16-18]。这在一定程度上是基于对唐氏综合症(DS)患者的研究，唐氏综合症患者在很小的年龄就出现了弥漫性斑块，在老年斑形成之前[19-21]。淀粉样前体沉积是抗Aβ抗体免疫反应阳性的“棉花样区域”，边界不规则，与少数营养不良的神经突起有关[16-18]。前淀粉样物不被刚果红或硫黄素S染色，超微结构主要由无定形、非纤维状物质组成。老年人可能有大量弥漫性斑块，没有任何神经元功能障碍或痴呆的迹象[22-24]。我们假设老年斑块的形成至少有两个主要步骤，Saβ首先经历构象变化并聚集成前叶样沉积，随后是一个多年逐渐致密和纤化的过程。只有在这种形式下，合成药物的显著毒性才被记录在案。
Alzheimer’s disease (AD) is neuropathologically defined by the deposition of amyloid in the form of senile plaques, congophilic angiopathy and neurofibrillary tangles (reviewed in [1]). The major constituent of both senile plaques and congophilic angiopathy is a 39–44 amino acid residue peptide, amyloid β (Aβ) [2–8]. Aβ is found, at low concentrations, as a normal constituent of biological fluids, where it is called soluble Aβ (sAβ) [9-12]. sAβ is predominantly Aβ1–40, although shorter and longer sequences exist, including Aβ1–28 and Aβ1–42 [13]. Neuritic plaque amyloid was first sequenced in 1985 [3] and was found to extend mainly to Aβ42}43, while vascular amyloid was initially reported to extend to Aβ1–28 [2] and later to Aβ 39}40 [5,14]. This heterogeneity at the C-terminus of Aβ was attributed to differences in the local tissue processing. More recent reports using different techniques have also found Aβ42 in vascular amyloid deposits [15]. Aβ in both types of amyloid deposits has a predominantly β-sheet structure; on the other hand, sAβ presumably is more random-coil and}or α-helical. An early stage in the development of senile plaques are ‘preamyloid’ or diffuse plaques [16–18]. This is based in part on studies in Down’s syndrome (DS) individuals, where diffuse plaques occur at a very early age, preceding the development of senile plaques [19–21]. Preamyloid deposits are ‘cotton-wool-like areas ’ that are immunoreactive with anti-Aβ antibodies, have irregular borders and are associated with few dystrophic neurites [16–18]. Preamyloid deposits are not stained by Congo Red or Thioflavine S, and ultrastructurally are composed mainly of amorphous, non-fibrillar material. Aged individuals can have large numbers of diffuse plaques without any signs of neuronal dysfunction or dementia [22–24]. We hypothesize that senile plaque formation can be viewed as having at least two major steps, whereby sAβ first undergoes a conformational change and aggregates into preamyloid deposits and this is followed by a gradual process of compaction and fibrillization over many years. It is only in this form that significant toxicity has been documented with synthetic