Intraperitoneal injection of amylin or its analog reduces Alzheimer’s disease (AD) pathology in the brains. However, self-injecting amylin analogs is difficult for patients due to cognitive deficits. This work aims to study the effects of amylin on the brain could be achieved by oral delivery as some study reported that amylin receptor may be present in the gastrointestinal tract. A 6-week course of oral amylin treatment reduced components of AD pathology, including the levels of amyloid-β, phosphorylated tau, and ionized calcium binding adaptor molecule 1. The treatment reduced active forms of cyclin-dependent kinase 5. Oral amylin treatment led to improvements in social deficit in AD mouse. Using immunofluorescence, we observed the amylin receptor complexed with the calcitonin receptor and receptor activity-modifying proteins in the enteric neurons. The study suggests the potential of the oral delivery of amylin analogs for the treatment of AD and other neurodegenerative diseases through enteric neurons.

腹腔注射胰岛淀粉样多肽或其类似物可减少大脑中的阿尔茨海默氏病（AD）病理。然而，由于认知缺陷，自我注射胰淀素类似物对于患者来说是困难的。这项工作旨在研究胰淀素对大脑的影响可以通过口服给药来实现，因为一些研究报道胰淀素受体可能存在于胃肠道中。为期 6 周的口服胰淀素治疗疗程可减少 AD 病理成分，包括淀粉样蛋白-β、磷酸化 tau 和离子化钙结合接头分子的水平 1。该治疗减少了细胞周期蛋白依赖性激酶的活性形式 5。口服胰淀素治疗导致改善 AD 小鼠的社交缺陷。使用免疫荧光，我们观察到肠神经元中胰岛淀粉样多肽受体与降钙素受体和受体活性修饰蛋白复​​合。该研究表明，口服胰淀素类似物通过肠神经元治疗 AD 和其他神经退行性疾病的潜力。