Pyroglutamate amyloid-β_3-42 (Aβ_pE3-42) is an N-terminally truncated and pyroglutamate-modified Aβ peptide retaining highly hydrophobic, amyloidogenic, and neurotoxic properties. In Alzheimer’s disease (AD) patients, Aβ_pE3-42 peptides accumulate into oligomers and induce cellular toxicity and synaptic dysfunction. Aβ_pE3-42 aggregates further seed the formation of amyloid plaques, which are the pathological hallmarks of AD. Given that Aβ_pE3-42 peptides play critical roles in the development of neurodegeneration, a reliable and reproducible synthetic access to these peptides may support pathological and medicinal studies of AD. Here, we synthesized Aβ_pE3-42 peptides through the microwave-assisted solid-phase peptide synthesis (SPPS). Utilizing thioflavin T fluorescence assay and dot blotting analysis with anti-amyloid oligomer antibody, the amyloidogenic activity of synthesized Aβ_pE3-42 peptides was confirmed. We further observed the cytotoxicity of Aβ_pE3-42 aggregates in cell viability test. To examine the cognitive deficits induced by synthetic Aβ_pE3-42 peptides, Aβ_pE3-42 oligomers were intracerebroventricularly injected into imprinting control region mice and Y-maze and Morris water maze tests were performed. We found that Aβ_pE3-42 aggregates altered the expression level of postsynaptic density protein 95 in cortical lysates. Collectively, we produced Aβ_pE3-42 peptides in the microwave-assisted SPPS and evaluated the amyloidogenic and pathological function of the synthesized peptides.

焦谷氨酸淀粉样蛋白-β _3-42 (Aβ _pE3-42 ) 是一种 N 末端截短的焦谷氨酸修饰的 Aβ 肽，具有高度疏水性、淀粉样蛋白形成和神经毒性特性。在阿尔茨海默病 (AD) 患者中，Aβ _pE3-42肽积聚成寡聚体并诱导细胞毒性和突触功能障碍。Aβ _pE3-42聚集体进一步引发淀粉样斑块的形成，这是 AD 的病理标志。鉴于 Aβ _pE3-42肽在神经变性的发展中起着关键作用，对这些肽的可靠且可重复的合成途径可能支持 AD 的病理学和医学研究。在这里，我们合成了 Aβ _pE3-42肽通过微波辅助固相肽合成（SPPS）。利用硫黄素 T 荧光测定和抗淀粉样蛋白寡聚体抗体的斑点印迹分析，证实了合成的 Aβ _pE3-42肽的淀粉样蛋白生成活性。_{我们在细胞活力测试中进一步观察了Aβ pE3-42}聚集体的细胞毒性。为了检查合成 Aβ _pE3-42肽诱导的认知缺陷，将 Aβ _pE3-42寡聚体脑室内注射到印记控制区小鼠中，并进行了 Y 迷宫和莫里斯水迷宫测试。我们发现 Aβ _pE3-42聚集体改变了皮质裂解物中突触后密度蛋白 95 的表达水平。总的来说，我们产生了 Aβ微波辅助 SPPS 中的_{pE3-42肽，并评估了合成肽的淀粉样蛋白生成和病理学功能。}