Evidence for lymphatic Aβ clearance in Alzheimer's transgenic mice.

Evidence for lymphatic Aβ clearance in Alzheimer's transgenic mice.
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DOI:
10.1016/j.nbd.2014.07.012
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发表时间:
2014-11
影响因子:
6.1
通讯作者:
Matsubara E
Matsubara E
中科院分区:
医学1区
文献类型:
--
作者:
Pappolla M;Sambamurti K;Vidal R;Pacheco-Quinto J;Poeggeler B;Matsubara E

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有证据表明,淋巴引流有助于清除大脑中的碎片,但其在淀粉样β肽(Aβ)积聚中的作用尚未得到证实。我们检测了不同年龄段阿尔茨海默病(AD)转基因模型中脑、血浆和淋巴结中各种形式Aβ的水平。在此,我们报告了一项新发现,即Aβ存在于AD转基因小鼠的颈部和腋窝淋巴结中,并且淋巴结中的Aβ水平随时间增加,反映了在大脑中观察到的Aβ水平增加。淋巴结中的Aβ水平显著高于血浆。15.5月龄时,淋巴结中单体可溶性Aβ40(p=0.003)和Aβ42(p=0.05)显著高于6月龄时测量的基线值。相比之下,血浆Aβ40水平无显著变化(p=0.68),血浆Aβ42水平在相同年龄显著下降(p=0.02)。在相同动物的脾淋巴组织和其他几种对照组织(包括心、肺、肝、肾和肠)中,Aβ浓度较低至不可检测,强烈表明淋巴结中的Aβ肽来源于脑。
Evidence has shown that lymphatic drainage contributes to removal of debris from the brain but its role in the accumulation of amyloid β peptides (Aβ) has not been demonstrated. We examined the levels of various forms of Aβ in the brain, plasma and lymph nodes in a transgenic model of Alzheimer’s disease (AD) at different ages. Herein, we report on the novel finding that Aβ is present in the cervical and axillary lymph nodes of AD transgenic mice and that Aβ levels in lymph nodes increase over time, mirroring the increase of Aβ levels observed in the brain. Aβ levels in lymph nodes were significantly higher than in plasma. At age 15.5 months, there was a significant increase of monomeric soluble Aβ40 (p=0.003) and Aβ42 (p=0.05) in the lymph nodes over the baseline values measured at 6 months of age. In contrast, plasma levels of Aβ40 showed no significant changes (p=0.68) and plasma levels Aβ42 significantly dropped (p=0.02) at the same age. Aβ concentration was low to undetectable in splenic lymphoid tissue and several other control tissues including heart, lung, liver, kidneys and intestine of the same animals, strongly suggesting that Aβ peptides in lymph nodes are derived from the brain.
人血浆中的β-淀粉样动力学。
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