Alzheimer’s disease (AD) is a neurodegenerative disorder, in which amyloid precursor protein (APP) misprocessing and tau protein hyperphosphorylation are well-established pathogenic cascades. Despite extensive considerations, the central mediator of neuronal cell death upon AD remains under debate. Therefore, we examined the direct interplay between tauopathy and amyloidopathy processes. We employed primary culture neurons and examined pathogenic P-tau and Aβ oligomers upon hypoxia treatment by immunofluorescence and immunoblotting. We observed both tauopathy and amyloidopathy processes upon the hypoxia condition. We also applied Aβ_1–42 or P-tau onto primary cultured neurons. We overexpressed P-tau in SH-SY5Y cells and found Aβ accumulation. Furthermore, adult male rats received Aβ_1–42 or pathogenic P-tau in the dorsal hippocampus and were examined for 8 weeks. Learning and memory performance, as well as anxiety behaviors, were assessed by Morris water maze and elevated plus-maze tests. Both Aβ_1–42 and pathogenic P-tau significantly induced learning and memory deficits and enhanced anxiety behavior after treatment 2 weeks. Aβ administration induced robust tauopathy distribution in the cortex, striatum, and corpus callosum as well as CA1. On the other hand, P-tau treatment developed Aβ oligomers in the cortex and CA1 only. Our findings indicate that Aβ_1–42 and pathogenic P-tau may induce each other and cause almost identical neurotoxicity in a time-dependent manner, while tauopathy seems to be more distributable than amyloidopathy.

阿尔茨海默病 (AD) 是一种神经退行性疾病，其中淀粉样前体蛋白 (APP) 错误加工和 tau 蛋白过度磷酸化是公认的致病级联反应。尽管进行了广泛的考虑，但 AD 后神经元细胞死亡的中心介质仍然存在争议。因此，我们研究了 tau 蛋白病和淀粉样蛋白病过程之间的直接相互作用。我们采用原代培养神经元，并通过免疫荧光和免疫印迹检测缺氧处理后的致病性 P-tau 和 Aβ 寡聚体。我们在缺氧条件下观察到 tau 蛋白病和淀粉样蛋白病过程。我们还将 Aβ _1-42或 P-tau应用于原代培养的神经元。我们在 SH-SY5Y 细胞中过表达 P-tau 并发现 Aβ 积累。此外，成年雄性大鼠接受了 Aβ _1-42或致病性 P-tau 在背海马体中，并进行了 8 周的检查。学习和记忆表现以及焦虑行为通过莫里斯水迷宫和高架十字迷宫测试进行评估。治疗 2 周后，Aβ _1-42和致病性 P-tau 均显着诱导学习和记忆缺陷并增强焦虑行为。Aβ 给药在皮层、纹状体和胼胝体以及 CA1 中诱导了强烈的 tau 蛋白病变分布。另一方面，P-tau 处理仅在皮层和 CA1 中产生 Aβ 寡聚体。我们的研究结果表明，Aβ _1-42和致病性 P-tau 可能相互诱导并以时间依赖性方式引起几乎相同的神经毒性，而 tau 蛋白病似乎比淀粉样蛋白病更易分布。