Institute for Regenerative Medicine (IREM), University of Zurich, Switzerland Neuroscience Center Zurich (ZNZ), Zurich, Switzerland.
Neurodegener Dis. 2018;18(1):49-56. doi: 10.1159/000486200. Epub 2018 Feb 7.
Strong genetic and epidemiological evidence points to a crucial role of the immune system in the development of Alzheimer disease (AD). CD3+ T lymphocytes have been described in brains of postmortem AD patients and in transgenic models of AD-like cerebral amyloidosis and tau pathology. However, the occurrence of T cells in AD brains is still controversial; furthermore, the relationship between T cells and hallmarks of AD pathology (amyloid plaques and neurofibrillary tangles) remains to be established.
We have studied the occurrence of T cells in postmortem hippocampi and mid frontal gyrus (MFG) samples of AD patients (Braak stage V-VI) and nondemented control subjects and correlated it with amyloid and tau pathology burden.
Confocal microscopy and bright-field immunohistochemistry were used to identify brain-associated T cells. Extravascular CD3+ T cells were quantified and compared to nondemented controls. In addition, numbers of extravascular CD3+ T cells were correlated with amyloid (6E10 staining) and tau pathology (AT8 staining) in the same sections.
Several CD3+, extravascular T cells were observed in the brains of AD patients, mostly of the CD8+ subtype. AD hippocampi harbored significantly increased numbers of extravascular CD3+ T cells compared to nondemented controls. CD3+ T cells significantly correlated with tau pathology but not with amyloid plaques in AD samples.
Our data support the notion of T-cell occurrence in AD brains and suggest that, in advanced stages of AD, T-cell extravasation is driven by tau-related neurodegenerative changes rather than by cerebral amyloidosis. T cells could be crucial for driving the amyloid-independent phase of the AD pathology.
强有力的遗传和流行病学证据表明免疫系统在阿尔茨海默病（AD）的发展中起着至关重要的作用。已经在 AD 患者死后的大脑和类似 AD 的脑淀粉样变性和 tau 病理学的转基因模型中描述了 CD3+T 淋巴细胞。然而，T 细胞在 AD 大脑中的发生仍然存在争议；此外，T 细胞与 AD 病理标志物（淀粉样斑块和神经原纤维缠结）之间的关系仍有待确定。
我们研究了 AD 患者（Braak 阶段 V-VI）死后海马体和中额回（MFG）样本中 T 细胞的发生情况，并将其与淀粉样蛋白和 tau 病理负担相关联。
使用共聚焦显微镜和明场免疫组织化学来鉴定脑相关 T 细胞。量化并比较脑外血管 CD3+T 细胞与无痴呆对照。此外，在相同切片中，将脑外血管 CD3+T 细胞的数量与淀粉样蛋白（6E10 染色）和 tau 病理学（AT8 染色）相关联。
在 AD 患者的大脑中观察到了多个 CD3+、脑外 T 细胞，主要是 CD8+亚型。AD 海马体中脑外 CD3+T 细胞的数量明显高于无痴呆对照组。在 AD 样本中，CD3+T 细胞与 tau 病理学显著相关，但与淀粉样斑块无关。
我们的数据支持 T 细胞在 AD 大脑中发生的观点，并表明在 AD 的晚期，T 细胞外渗是由 tau 相关的神经退行性变化驱动的，而不是由脑淀粉样变性引起的。T 细胞可能对驱动 AD 病理学的淀粉样蛋白非依赖性阶段至关重要。
