Amyloid-β deposits in the cerebral cortex of the aged common marmoset (Callithrix jacchus):: incidence and chemical composition

Amyloid-β deposits in the cerebral cortex of the aged common marmoset (Callithrix jacchus):: incidence and chemical composition
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DOI:
10.1007/s004010100429
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发表时间:
2002-01-01
影响因子:
12.7
通讯作者:
Wu, CK
Wu, CK
中科院分区:
医学1区
文献类型:
--
作者:
Geula, C;Nagykery, N;Wu, CK

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研究了低等灵长类动物普通狨猴(Callithrix jacchus)中淀粉样蛋白β(Abeta)肽阳性沉积物的发生率、分布和化学成分。在7岁以下的7只绒猴脑中未观察到Abeta沉积。在15只7岁以上的绒猴中,60%显示皮质A β免疫反应性斑块,80%有A β沉积在皮质内血管中,87%显示A β沉积在脑膜血管中。年龄最大的动物(15岁)的大脑皮层含有大量的沉积物。A β免疫反应斑块主要发现在联合皮质区,其次是低密度的边缘皮质区。血管内沉积物最常见于枕叶皮质。A β 40主要存在于血管沉积物中,而A β 42存在于斑块中。大约20%的斑块和大多数血管沉积物显示硫磺素S染色,表明存在纤维状A β。不同比例的A β沉积物含有乙酰胆碱酯酶或丁酰胆碱酯酶活性和载脂蛋白E和α 1-抗糜蛋白酶免疫反应性。在肿胀的神经突中,少数斑块含有淀粉样前体蛋白的免疫反应性。然而,在这些神经突中没有异常磷酸化的tau蛋白免疫反应性。对一群绒猴的生存分析表明,只有6%的动物可以存活超过7岁。这些结果表明,老化的绒猴大脑显示Abeta沉积物的分布和化学组成与人类相似。这些相似性表明,老年绒猴可能是一个有用的较低的灵长类动物模型的病理影响的研究。然而,预期达到老年的动物数量相对较少,严重限制了该物种作为Abeta沉积模型的实用性。
The incidence, distribution and chemical composition of amyloid-beta (Abeta) peptide-positive deposits were investigated in the lower primate species common marmoset (Callithrix jacchus). No Abeta deposits were observed in the brains of 7 marmosets below 7 years of age. In 15 marmosets above 7 years, 60% displayed cortical Abeta-immunoreactive plaques, 80% had Abeta deposited in intracortical vessels and 87% displayed Abeta deposits in meningeal vessels. The cerebral cortex of the oldest animal (15 years) contained a substantial density of deposits. Abeta-immunoreactive plaques were found predominantly in association cortical zones followed by a lower density in paralimbic cortical areas. Deposits within vessels were most frequent in occipital cortex. Abeta40 was found primarily in vascular deposits, while Abeta42 was present in plaques. Approximately 20% of plaques and most vascular deposits displayed thioflavin S staining, indicative of the presence of fibrillar Abeta. Varying proportions of Abeta deposits contained acetylcholinesterase or butyrylcholinesterase activities and apolipoprotein E and alpha1-antichymotrypsin immunoreactivity. A few plaques contained immunoreactivity for amyloid precursor protein in swollen neurites. However, no abnormally phosphorylated tau immunoreactivity was present in these neurites. Survival analysis in a colony of marmosets indicated that only 6% of animals can be expected to survive beyond 7 years of age. These results indicate that the aged marmoset brain displays Abeta deposits with a distribution and chemical composition similar to those found in the human. These similarities suggest that the aged marmoset may be a useful lower primate model for the study of the pathological effects of Abeta. However, the relatively small number of animals which can be expected to reach old age severely limits the utility of this species as a model of Abeta deposition.