Evidence for lymphatic Aβ clearance in Alzheimer's transgenic mice

NEUROBIOLOGY OF DISEASE

卷:71

Article

Pappolla, Miguel¹  Sambamurti, Kumar²  Vidal, Ruben³  Pacheco-Quinto, Javier⁴  Poeggeler, Burkhard⁵  Matsubara, Etsuro⁶ 

[1] Univ Texas Med Branch, Dept Neurol, Galveston, TX 77555 USA

[2] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA

[3] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA

[4] Mid Atlantic Neonatol Associates & Atlantic Hlth, Biomed Res Inst New Jersey, Morristown, NJ 07960 USA

[5] Univ Gottingen, Fac Biol & Psychol, D-37073 Gottingen, Germany

[6] Hirosaki Univ, Grad Sch Med, Inst Brain Sci, Dept Neurol, Aomori, Japan

关键词: Lymph node;    Amyloid beta protein;    Alzheimer's disease;    Protein clearance;   

DOI  :  10.1016/j.nbd.2014.07.012

来源: Elsevier

【 摘 要 】

Evidence has shown that lymphatic drainage contributes to removal of debris from the brain but its role in the accumulation of amyloid beta peptides (A beta) has not been demonstrated. We examined the levels of various forms of A beta 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 A beta is present in the cervical and axillary lymph nodes of AD transgenic mice and that A beta levels in lymph nodes increase over time, mirroring the increase of A beta levels observed in the brain. A beta levels in lymph nodes were significantly higher than in plasma. At age 15.5 months, there was a significant increase of monomeric soluble A beta 40 (p = 0.003) and A beta 42 (p = 0.05) in the lymph nodes over the baseline values measured at 6 months of age. In contrast, plasma levels of A beta 40 showed no significant changes (p = 0.68) and plasma levels A beta 42 significantly dropped (p = 0.02) at the same age. A beta 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 A beta peptides in lymph nodes are derived from the brain. (C) 2014 Elsevier Inc. All rights reserved.

【 授权许可】

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