Abstract：
Alzheimer\'s disease (AD) is the most common neurodegenerative disorder that affects the cerebral cortex and hippocampus, and is characterised by progressive cognitive decline and memory loss. A recent report of a patient carrying a novel gain-of-function variant of RELN (H3447R, termed RELN-COLBOS) who developed resilience against presenilin-linked autosomal-dominant AD (ADAD) has generated enormous interest. The RELN-COLBOS variant enhances interactions with the apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor (VLDLR), which are associated with delayed AD onset and progression. These findings were validated in a transgenic mouse model. Reelin is involved in neurodevelopment, neurogenesis, and neuronal plasticity. The evidence accumulated thus far has demonstrated that the Reelin pathway links apolipoprotein E4 (ApoE4), amyloid-β (Aβ), and tubulin-associated unit (Tau), which are key proteins that have been implicated in AD pathogenesis. Reelin and key components of the Reelin pathway have been highlighted as potential therapeutic targets and biomarkers for AD.
摘要：
阿尔茨海默病（AD）是影响大脑皮层和海马的最常见的神经退行性疾病，以进行性认知衰退和记忆力减退为特征。最近有报道称，一名患者携带了一种新型的RELN功能增益变体(H3447R，称为RELN-COLBOS）的人对早老素相关的常染色体显性遗传AD（ADAD）产生了极大的兴趣。RELN-CORBOS变体增强与载脂蛋白E受体2（ApoER2）和极低密度脂蛋白受体（VLDLR）的相互作用，这与AD的延迟发作和进展有关。这些发现在转基因小鼠模型中得到验证。Reelin参与神经发育,神经发生，和神经元可塑性。迄今为止积累的证据表明，Reelin途径连接载脂蛋白E4（ApoE4），淀粉样蛋白-β（Aβ），和微管蛋白相关单元(Tau)，是与AD发病机制有关的关键蛋白。Reelin和Reelin途径的关键组分已被强调为AD的潜在治疗靶标和生物标志物。
