Reactivation of HSV-1 in the brain of patients with familial Alzheimer's disease
Reactivation of HSV-1 in the brain of patients with familial Alzheimer's disease
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DOI：
10.1002/jmv.20133
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发表时间：
2004-08-01
影响因子：
12.7
通讯作者：
Nishiyama, Y
中科院分区：
文献类型：
--
作者：
Mori, I;Kimura, Y;Nishiyama, Y
1 型单纯疱疹病毒 (HSV-1) 已被提议作为散发性阿尔茨海默病的环境危险因素，尽管这个问题仍存在争议。 HSV-1 与家族性阿尔茨海默病（一种罕见的阿尔茨海默病）发病机制的关系尚未得到解决。我们研究了三名家族性阿尔茨海默病患者的福尔马林固定、石蜡包埋的死后脑组织切片中是否存在 HSV-1 DNA。巢式聚合酶链反应 (PCR) 在所有 3 名家族性阿尔茨海默病患者的大脑中检测到 HSV-1 糖蛋白 D 基因，优先在额叶和颞叶皮质中检测，而 6 名年龄匹配的非阿尔茨海默病患者中只有 1 例能够揭示 HSV1 基因的存在。 PCR检测到两名散发性阿尔茨海默病患者的额叶皮层中存在HSV-1 DNA。 HSV-1 的存在与大脑皮层中的 β-淀粉样蛋白沉积有关。为了阐明HSV-1在家族性阿尔茨海默病患者脑组织中的定位，使用了酪酰胺信号放大系统的原位杂交。它以点状染色方式主要在皮质神经元的细胞质中检测到 HSV-1 特异性信号。此外，高灵敏度免疫组织化学显示皮质神经元细胞质中存在HSV-1抗原。该报告提供了家族性阿尔茨海默氏病患者大脑中 HSV-1 重新激活的第一个证据，与 a-淀粉样蛋白沉积相关，并表明 HSV-1 可能与遗传因素一起参与家族性阿尔茨海默氏病的发病机制。 (C) 2004 Wiley-Liss, Inc.
Herpes simplex virus type 1 (HSV-1) has been proposed as an environmental risk factor for sporadic Alzheimer's disease, although this issue is still in dispute. The involvement of HSV-1 in the pathogenesis of familial Alzheimer's disease, the uncommon type of Alzheimer's disease, has not been addressed yet. We investigated formalin-fixed, paraffin-embedded, postmortem brain tissue sections of three patients with familial Alzheimer's disease for the presence of HSV-1 DNA. The nested polymerase chain reaction (PCR) detected the HSV-1 glycoprotein D gene in the brain of all three patients with familial Alzheimer's disease preferentially in the frontal and temporal cortices, whereas only one case out of six age-matched, non-Alzheimer's disease individuals could disclose the presence of HSV1 gene. The PCR detected HSV-1 DNA in the frontal cortex of the two patients with sporadic Alzheimer's disease. The presence of HSV-1 was associated with beta-amyloid deposition in the cerebral cortex. To clarify the localization of HSV-1 in the brain tissue of patients with familial Alzheimer's disease, the in situ hybridization of the tyramide signal amplification system was used. It detected the HSV-1-specific signals predominantly in the cytoplasm of cortical neurons in a dot-like staining fashion. In addition, high-sensitivity immunohistochemistry revealed the existence of HSV-1 antigens in the cytoplasm of cortical neurons. This report provides the first evidence of reactivation of HSV-1 in the brain of patients with familial Alzheimer's disease, associated with a-amyloid deposition, and suggests the possible involvement of HSV-1 together with genetic factors in the pathogenesis of familial Alzheimer's disease. (C) 2004 Wiley-Liss, Inc.