Amyloid-beta peptide and oligomers in the brain and cerebrospinal fluid of aged canines.
Amyloid-beta peptide and oligomers in the brain and cerebrospinal fluid of aged canines.
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DOI：
10.3233/jad-2010-1397
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发表时间：
2010
期刊：
影响因子：
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通讯作者：
Murphy MP
中科院分区：
文献类型：
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作者：
Head E;Pop V;Sarsoza F;Kayed R;Beckett TL;Studzinski CM;Tomic JL;Glabe CG;Murphy MP
阿尔茨海默病（AD）发病机制的研究需要使用在脑中产生一定量的淀粉样病变的动物模型。老年犬（比格犬）自然积累人型淀粉样β肽（Aβ），并出现认知功能的平行下降。然而，脑和脑脊液（CSF）中生化提取的Aβ的类型和数量，其与衰老的联系以及与人类衰老的相似性尚未得到系统研究。研究了30只4.5-15.7岁的比格犬。用ELISA法检测脑脊液中Aβ40和Aβ42的含量，并从SDS和甲酸提取的前额叶皮质中检测Aβ40和Aβ42的含量。用于评估免疫组织化学淀粉样蛋白负荷的对侧半球样品用于比较。在大脑中，在较年轻时检测到Aβ42的增加，在Aβ40增加之前，并且与淀粉样蛋白负荷增加相关。在CSF中，Aβ42随年龄增长而降低，而Aβ40水平保持不变。CSF Aβ42/40比值也是脑中Aβ含量的良好预测因子。CSF中可溶性低聚物的量与脑可提取Aβ呈负相关，而脑中低聚物与SDS可溶性Aβ42相关。这些发现表明，老年犬大脑中的Aβ表现出与人类大脑中沉积的Aβ相对应的模式。这些相似之处支持了这样的观点，即老年犬是转基因小鼠和人类之间的有用中间体，用于研究淀粉样蛋白病理学的发展，并且是改进治疗干预的潜在有用模型。
The study of Alzheimer’s disease (AD) pathogenesis requires the use of animal models that develop some amount of amyloid pathology in the brain. Aged canines (beagles) naturally accumulate human-type amyloid β-peptide (Aβ) and develop parallel declines in cognitive function. However, the type and quantity of biochemically extracted Aβ in brain and cerebrospinal fluid (CSF), its link to aging and similarity to human aging, has not been examined systematically. Thirty beagles, aged 4.5–15.7 years, were studied. Aβ40 and Aβ42 were measured in CSF by ELISA, and from SDS and formic acid extracted prefrontal cortex. A sample of the contralateral hemisphere, used to assess immunohistochemical amyloid load, was used for comparison. In the brain, increases in Aβ42 were detected at a younger age, prior to increases in Aβ40, and were correlated with an increased amyloid load. In the CSF, Aβ42 decreased with age while Aβ40 levels remained constant. The CSF Aβ42/40 ratio was also a good predictor of the amount of Aβ in the brain. The amount of soluble oligomers in CSF was inversely related to brain extractable Aβ, whereas oligomers in the brain were correlated with SDS soluble Aβ42. These findings indicate that the Aβ in the brain of the aged canine exhibits patterns that mirror Aβ deposited in the human brain. These parallels support the idea that the aged canine is a useful intermediate between transgenic mice and humans for studying the development of amyloid pathology, and is a potentially useful model for the refinement of therapeutic interventions.