Cerebral amyloid-beta protein accumulation with aging in cotton-top tamarins: A model of early Alzheimer's disease?
Cerebral amyloid-beta protein accumulation with aging in cotton-top tamarins: A model of early Alzheimer's disease?
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DOI：
10.1089/rej.2008.0677
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发表时间：
2008-04-01
影响因子：
2.6
通讯作者：
Mansfield, Keith G.
中科院分区：
文献类型：
--
作者：
Lemere, Cynthia A.;Oh, Jiwon;Mansfield, Keith G.
阿尔茨海默病（AD）是老年人中最常见的进行性痴呆形式。AD的两个主要神经病理学标志包括淀粉样β蛋白（A β）在斑块和血管中的脑沉积，以及脑中神经元缠结的存在。此外，活化的小胶质细胞和反应性星形胶质细胞通常与斑块和缠结相关。许多其他蛋白质与人类AD脑中的斑块相关，包括Apo E和泛素。淀粉样前体蛋白及其较短片段A β在人类和非人类灵长类动物之间是同源的。先前已报告恒河猴、长尾猴、松鼠猴、绒猴、狐猴、食蟹猴、黑猩猩和猩猩的脑A β沉积。在这里，我们报告，为第一次，年龄相关的神经病理学变化的棉顶绢毛猴（CTT，Saguinus俄狄浦斯），濒危的非人类灵长类动物原产于哥伦比亚和哥斯达黎加的热带雨林。在野外的典型寿命为13-14岁，在圈养中为15-20岁。我们进行了详细的免疫组织化学分析的A β沉积和相关的发病机制，存档脑切片从36个绢毛猴年龄范围从6-21岁。在20只年龄最大的绢毛猴（>12岁）中的16只中观察到β斑块沉积。斑块主要含有A β 42，在最老的动物中，与反应性星形胶质细胞、活化的小胶质细胞、Apo E和泛素阳性营养不良性神经突相关，与人类斑块相似。在20只老年绢毛猴中的14只中检测到血管A β; A β 42先于A β 40沉积。磷酸-tau标记的营养不良性神经突和缠结，通常存在于人AD中，在绢毛猴中不存在。总之，绢毛猴可能代表了早期AD病理学的模型。
Alzheimer's disease (AD) is the most common progressive form of dementia in the elderly. Two major neuropathological hallmarks of AD include cerebral deposition of amyloid-beta protein (A beta) into plaques and blood vessels, and the presence of neurofibrillary tangles in brain. In addition, activated microglia and reactive astrocytes are often associated with plaques and tangles. Numerous other proteins are associated with plaques in human AD brain, including Apo E and ubiquitin. The amyloid precursor protein and its shorter fragment, A beta, are homologous between humans and non-human primates. Cerebral A beta deposition has been reported previously for rhesus monkeys, vervets, squirrel monkeys, marmosets, lemurs, cynomologous monkeys, chimpanzees, and orangutans. Here we report, for the first time, age-related neuropathological changes in cotton-top tamarins (CTT, Saguinus oedipus), an endangered non-human primate native to the rainforests of Colombia and Costa Rica. Typical lifespan is 13-14 years of age in the wild and 15-20+ Years in captivity. We performed detailed immunohistochemical analyses of A beta deposition and associated pathogenesis in archived brain sections from 36 tamarins ranging in age from 6-21 years. A beta plaque deposition was observed in 16 of the 20 oldest tamarins (>12 years). Plaques contained mainly A beta 42, and in the oldest animals, were associated with reactive astrocytes, activated microglia, Apo E, and ubiquitin-positive dystrophic neurites, similar to human plaques. Vascular A beta was detected in 14 of the 20 aged tamarins; A beta 42 preceded A beta 40 deposition. Phospho-tau labeled dystrophic neurites and tangles, typically present in human AD, were absent in the tamarins. In conclusion, tamarins may represent a model of early AD pathology.