外周给予错误折叠的 Aβ 聚集物导致脑淀粉样蛋白病理的传播。

Transmission of cerebral amyloid pathology by peripheral administration of misfolded Aβ aggregates.

机构信息

Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Centro integrativo de biología y química aplicada (CIBQA), Universidad Bernardo O'Higgins, Santiago, Chile.

出版信息

Mol Psychiatry. 2021 Oct;26(10):5690-5701. doi: 10.1038/s41380-021-01150-w. Epub 2021 May 17.

Abstract

Previous reports showed that brain Aβ amyloidosis can be induced in animal models by exogenous administration of pre-formed aggregates. To date, only intra-peritoneal and intra-venous administrations are described as effective means to peripherally accelerate brain Aβ amyloidosis by seeding. Here, we show that cerebral accumulation of Aβ can be accelerated after exposing mouse models of Alzheimer's disease (AD) to Aβ seeds by different peripheral routes of administration, including intra-peritoneal and intra-muscular. Interestingly, animals receiving drops of brain homogenate laden with Aβ seeds in the eyes were efficiently induced. On the contrary, oral administration of large quantities of brain extracts from aged transgenic mice and AD patients did not have any effect in brain pathology. Importantly, pathological induction by peripheral administration of Aβ seeds generated a large proportion of aggregates in blood vessels, suggesting vascular transport. This information highlights the role of peripheral tissues and body fluids in AD-related pathological changes.

摘要

先前的报告表明,通过外源性给予预先形成的聚集物,可以在动物模型中诱导脑 Aβ 淀粉样蛋白病。迄今为止,只有腹腔内和静脉内给药被描述为通过播种有效地在周围加速脑 Aβ 淀粉样蛋白病的手段。在这里,我们表明,通过不同的外周给药途径,包括腹腔内和肌肉内,将 Aβ 种子暴露于阿尔茨海默病 (AD) 小鼠模型后,Aβ 在大脑中的积累可以加速。有趣的是,眼睛滴注载有 Aβ 种子的脑匀浆的动物被有效地诱导。相反,大量口服来自老年转基因小鼠和 AD 患者的脑提取物对大脑病理学没有任何影响。重要的是,外周给予 Aβ 种子的病理性诱导在血管中产生了大量的聚集物,提示血管转运。这些信息突出了外周组织和体液在 AD 相关病理变化中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bea/8595465/c295df833f26/nihms-1697848-f0001.jpg

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