Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β (Aβ) which ultimately forms plaques. These Aβ deposits can be induced in APP transgenic mouse models by prion-like seeding. It has been widely accepted that anosmia and hyposmia occur during the early stages of AD, even before cognitive deficits are present. In order to determine the impact of seed-induced Aβ deposits on olfaction, we performed intracerebral injections of seed-competent brain homogenate into the olfactory bulb of young pre-depositing APP transgenic mice. Remarkably, we observed a dramatic olfactory impairment in those mice. Furthermore, the number of newborn neurons as well as the activity of cells in the mitral cell layer was decreased. Notably, exposure to an enriched environment reduced Aβ seeding, vivified neurogenesis and most importantly reversed olfactory deficits. Based on our findings, we conclude that altered neuronal function as a result of induced Aβ pathology might contribute to olfactory dysfunction in AD.

阿尔茨海默病 (AD) 的特征是淀粉样蛋白-β (Aβ) 的积累，最终形成斑块。这些 Aβ 沉积物可以通过朊病毒样接种在 APP 转基因小鼠模型中诱导。人们普遍认为，嗅觉丧失和嗅觉减退发生在 AD 的早期阶段，甚至在出现认知缺陷之前。为了确定种子诱导的 Aβ 沉积物对嗅觉的影响，我们将种子活性脑匀浆脑内注射到年轻的预沉积 APP 转基因小鼠的嗅球中。值得注意的是，我们在这些小鼠身上观察到明显的嗅觉障碍。此外，新生神经元的数量以及二尖瓣细胞层中细胞的活性降低。值得注意的是，暴露于丰富的环境会减少 Aβ 的播种，激活神经发生，最重要的是逆转嗅觉缺陷。根据我们的发现，我们得出结论，诱导的 Aβ 病理学导致的神经元功能改变可能导致 AD 中的嗅觉功能障碍。