The onset of Alzheimer's disease (AD) is triggered by the aggregation of amyloid β (Aβ) peptides which leads to the formation of fibrils. Molecules that are able to inhibit fibrillation and/or disrupt fibrils have aroused interest for AD therapy. Fibrillation is a complex process highly dependent on the surrounding environment. One of the most relevant factors affecting Aβ aggregation is the presence of cellular membranes. Here, the ability of caffeic acid (CA) in preventing the Aβ_1-42 aggregation and disaggregating mature fibrils was evaluated in a membrane-like environment and in a bulk solution for comparison. To this end, liposomes were used as in vitro models of neuronal membranes. CA exhibited strong activity in inhibiting the fibrillation of Aβ_1-42 in the aqueous medium, which remained in the presence of liposomes. Furthermore, CA disrupted instantly preformed fibrils in the aqueous medium. However, the CA's disaggregating activity was disturbed by the presence of lipid membranes. Instead of being immediate, the CA's disaggregating activity increased over time. The moderate affinity of CA for the lipid bilayer may explain the distinct fibrils disaggregation profiles. These findings emphasize the therapeutic potential of CA in preventing and treating AD, thus justifying further investigations in animal models.

阿尔茨海默病 (AD) 的发病是由淀粉样蛋白 β (Aβ) 肽的聚集引发的，从而导致原纤维的形成。能够抑制原纤维形成和/或破坏原纤维的分子引起了对 AD 治疗的兴趣。纤维化是一个高度依赖于周围环境的复杂过程。影响 Aβ 聚集的最相关因素之一是细胞膜的存在。在这里，咖啡酸 (CA) 在防止 Aβ _1-42聚集和分解成熟原纤维方面的能力在膜状环境和大量溶液中进行了评估以进行比较。为此，脂质体被用作神经元膜的体外模型。CA 在抑制 Aβ _1-42的纤颤方面表现出很强的活性在存在脂质体的情况下保持在水性介质中。此外，CA 立即破坏了水性介质中的预形成原纤维。然而，CA 的分解活性受到脂质膜的干扰。CA 的分解活动并没有立即发生，而是随着时间的推移而增加。CA 对脂质双层的中等亲和力可以解释不同的原纤维分解曲线。这些发现强调了 CA 在预防和治疗 AD 方面的治疗潜力，从而证明在动物模型中进行进一步研究是合理的。