Department of Neurology, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX 77030, USA.
Dpto. Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga-IBIMA, Facultad de Ciencias, Universidad of Malaga, 29010 Malaga, Spain.
Cells. 2022 Oct 31;11(21):3442. doi: 10.3390/cells11213442.
Extensive experimental and human-derived evidence suggest that misfolded Aβ particles spread similarly to infectious prions. Moreover, peripheral administration of Aβ seeds accelerates brain amyloidosis in both susceptible experimental animals and humans. The mechanisms and elements governing the transport of misfolded Aβ from the periphery to the brain are not fully understood, although circulation and retrograde axonal transport have been proposed. Here, we demonstrate that injection of Aβ seeds in the tongue, a highly innervated organ, substantially accelerates the appearance of plaques in Tg2576 mice. In addition, the extra-nasal exposure of Aβ aggregates increased amyloid pathology in the olfactory bulb. Our results show that exposing highly innervated tissues to Aβ seeds accelerates AD-like pathological features, and suggest that Aβ seeds can be transported from peripheral compartments to the brain by retrograde axonal transport. Research in this direction may be relevant on different fronts, including disease mechanisms, diagnosis, and risk-evaluation of potential iatrogenic transmission of Aβ misfolding.
大量的实验和人体研究证据表明，错误折叠的 Aβ 颗粒的传播方式类似于传染性朊病毒。此外，外周给予 Aβ 种子会加速易感实验动物和人类的脑内淀粉样变性。虽然已经提出了循环和逆行轴突运输，但对于错误折叠的 Aβ 从外周向大脑转运的机制和元素还不完全了解。在这里，我们证明，在舌部（一个高度神经支配的器官）注射 Aβ 种子会显著加速 Tg2576 小鼠斑块的出现。此外，鼻外暴露于 Aβ 聚集物会增加嗅球中的淀粉样病理。我们的研究结果表明，将高度神经支配的组织暴露于 Aβ 种子会加速 AD 样病理特征，并且表明 Aβ 种子可以通过逆行轴突运输从外周隔室转运到大脑。这一方向的研究可能在不同方面具有相关性，包括疾病机制、诊断和潜在的医源性 Aβ 错误折叠传播的风险评估。
