Molecular approaches to the treatment, prophylaxis, and diagnosis of Alzheimer's disease: tangle formation, amyloid-β, and microglia in Alzheimer's disease.
Molecular approaches to the treatment, prophylaxis, and diagnosis of Alzheimer's disease: tangle formation, amyloid-β, and microglia in Alzheimer's disease.
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DOI：
10.1254/jphs.11r10fm
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发表时间：
2012
影响因子：
3.5
通讯作者：
K. Takata;Y. Kitamura
中科院分区：
文献类型：
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作者：
K. Takata;Y. Kitamura
阿尔茨海默病 (AD) 的病理特征包括老年斑、神经原纤维缠结 (NFT)、突触丧失和神经变性。老年斑由β淀粉样蛋白（Aβ）组成，周围有小胶质细胞，小胶质细胞是中枢神经系统中的主要免疫效应细胞。 NFT 是由过度磷酸化 tau 蛋白在神经元内积累形成的，进行性突触和神经元损失与 AD 的认知缺陷密切相关。对家族性 AD 的相关基因和唐氏综合症（21 三体）患者大脑病理变化的时间模式的研究表明，Aβ 积累是影响其他 AD 病理的主要事件，唐氏综合症患者总是出现 AD 的神经病理学。尽管 AD 病理之间相互作用的细节仍不清楚，但讨论这个问题的实验证据已经积累起来。在本文中，我们回顾并讨论了将 AD 病理学相互联系起来的最新发现。对 AD 大脑中诱发的病理之间相互作用的进一步研究可能有助于深入了解 AD 的发病机制，并开发新的 AD 治疗、预防和早期诊断策略。
Pathological hallmarks of Alzheimer's disease (AD) include senile plaques, neurofibrillary tangles (NFTs), synaptic loss, and neurodegeneration. Senile plaques are composed of amyloid-β (Aβ) and are surrounded by microglia, a primary immune effector cell in the central nervous system. NFTs are formed by the intraneuronal accumulation of hyperphosphorylated tau, and progressive synaptic and neuronal losses closely correlate with cognitive deficits in AD. Studies on responsible genes of familial AD and temporal patterns of pathological changes in brains of patients with Down's syndrome (Trisomy 21), who invariably develop neuropathology of AD, have suggested that Aβ accumulation is a primary event that influences other AD pathologies. Although details of the interaction between AD pathologies remain unclear, experimental evidences to discuss this issue have been accumulated. In this paper, we review and discuss recent findings that link the AD pathologies to each other. Further studies on the interaction between pathologies induced in AD brain may contribute to provide deep insight into the pathogenesis of AD and to develop novel therapeutic, prophylactic, and early diagnostic strategies for AD.