在老年猫的大脑中，一种无淀粉样蛋白沉积的 4R tau 病发生发展。

A 4R tauopathy develops without amyloid deposits in aged cat brains.

机构信息

Laboratory of Anatomy, Biomechanics and Organogenesis, ULB neuroscience institute, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.

Laboratory of Histology, Neuroanatomy and Neuropathology, ULB Neuroscience Institute, Université Libre de Bruxelles, Faculty of Medicine, Brussels, Belgium.

出版信息

Neurobiol Aging. 2019 Sep;81:200-212. doi: 10.1016/j.neurobiolaging.2019.05.024. Epub 2019 Jun 14.

DOI:10.1016/j.neurobiolaging.2019.05.024

PMID:31306814

Abstract

Human tauopathies are neurodegenerative diseases with accumulation of abnormally phosphorylated and aggregated tau proteins forming neurofibrillary tangles. We investigated the development of tau pathology in aged cat brains as a model of neurofibrillary tangle formation occurring spontaneously during aging. In 4 of 6 cats aged between 18 and 21 years, we found a somatodendritic accumulation of phosphorylated and aggregated tau in neurons and oligodendrocytes. Two of these 4 cats had no amyloid immunoreactivity. These tau inclusions were mainly composed of 4R tau isoforms and straight filaments and colocalized with the active form of the glycogen synthase kinase-3 (GSK3). Cat brains with a tau pathology showed a significant cortical atrophy and neuronal loss. We demonstrate in this study the presence of a tau pathology in aged cat brains that develop independently of amyloid deposits. The colocalization of the active form of the GSK3 with tau inclusions as observed in human tauopathies suggests that this kinase could be responsible for the abnormal tau phosphorylation observed in aged cat brains, representing a mechanism of tau pathology development shared between a naturally occurring tauopathy in aged cats and human tauopathies.

摘要

人类 tau 病是神经退行性疾病，其特征是异常磷酸化和聚集的 tau 蛋白积累，形成神经纤维缠结。我们研究了老年猫脑中 tau 病理学的发展，作为在衰老过程中自发发生的神经纤维缠结形成的模型。在 6 只年龄在 18 至 21 岁的猫中，我们发现神经元和少突胶质细胞中有磷酸化和聚集的 tau 的体树突积累。这 4 只猫中有 2 只没有淀粉样蛋白免疫反应性。这些 tau 包含物主要由 4R tau 异构体和直丝组成，并与糖原合酶激酶-3（GSK3）的活性形式共定位。具有 tau 病理学的猫脑表现出明显的皮质萎缩和神经元丧失。在这项研究中，我们证明了在老年猫脑中存在 tau 病理学，其发展与淀粉样蛋白沉积无关。在人类 tau 病中观察到的 GSK3 的活性形式与 tau 包含物的共定位表明，这种激酶可能负责观察到的老年猫脑中异常 tau 磷酸化，代表了一种在自然发生的老年猫 tau 病和人类 tau 病之间共享的 tau 病理学发展机制。