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首页> 外文期刊>The FASEB Journal >Amyloid-beta and islet amyloid pathologies link Alzheimer's disease and type 2 diabetes in a transgenic model
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Amyloid-beta and islet amyloid pathologies link Alzheimer's disease and type 2 diabetes in a transgenic model

机译:β淀粉样蛋白和胰岛淀粉样蛋白病理学在转基因模型中将阿尔茨海默病和2型糖尿病联系起来

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Alzheimer's disease (AD) and type 2 diabetes (T2D) present a significant risk to each other. AD and T2D are characterized by deposition of cerebral amyloid-beta (A beta) and pancreatic human islet amyloid polypeptide (hIAPP), respectively. We investigated the role of amyloidogenic proteins in the interplay between these diseases. A novel double transgenic mouse model combining T2D and AD was generated and characterized. AD-related amyloid transgenic mice coexpressing hIAPP displayed peripheral insulin resistance, hyperglycemia, and glucose intolerance. A beta and IAPP amyloidco-deposition increased tau phosphorylation, and a reduction in pancreatic beta-cell mass was detected inislets. Increased brain A beta deposition and tau phosphorylation and reduced insulin levels and signaling were accompanied by extensive synaptic loss and decreased neuronal counts. Ab immunization rescued the peripheral insulin resistance and hyperglycemia, suggesting a role for A beta in T2D pathogenesis for individuals predisposed to AD. These findings demonstrate that Ab and IAPP are key factors in the overlapping pathologies of AD and T2D.
机译:阿尔茨海默病 (AD) 和 2 型糖尿病 (T2D) 对彼此都存在重大风险。AD 和 T2D 的特征分别是脑淀粉样蛋白-β (A β) 和胰岛人胰岛淀粉样蛋白多肽 (hIAPP) 的沉积。我们研究了淀粉样蛋白在这些疾病之间的相互作用中的作用。生成并表征了一种结合T2D和AD的新型双转基因小鼠模型。共表达hIAPP的AD相关淀粉样蛋白转基因小鼠表现出外周胰岛素抵抗、高血糖和葡萄糖耐受不良。β 和 IAPP 淀粉样蛋白共沉积增加了 tau 磷酸化,并且在胰岛检测到胰腺 β 细胞质量减少。脑 A β 沉积和 tau 磷酸化增加以及胰岛素水平和信号传导降低伴随着广泛的突触丢失和神经元计数减少。抗体免疫挽救了外周胰岛素抵抗和高血糖,表明 A β 在易患 AD 的个体的 T2D 发病机制中起作用。这些发现表明,Ab和IAPP是AD和T2D病理重叠的关键因素。

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