生物发光成像在癌症和其他疾病的临床前研究中的日常实践在过去的几十年里发生了变化；然而，在阿尔茨海默病（AD）的临床前研究中，几乎没有应用生物发光成像。在本文中，我们证明了生物发光成像可以用于报告体内淀粉样 β（Aβ）物种的水平。我们假设，新发现的荧光素酶底物AkaLumine可以与Aβ聚集物和斑块结合。我们进一步推测Aβ聚集物/纤维/斑块可以被视为“功能性淀粉样物质”，具有储备功能，以固定和释放AkaLumine来控制生物发光强度，从而能够报告Aβ的水平。我们的假设通过体外溶液测试、脑组织和小鼠的模拟研究、AD小鼠的双光子成像和多光子成像以及使用AkaLuciferase（AkaLuc）对转基因AD小鼠进行病毒转导的体内生物发光成像得到了验证。结果与预期一致，与对照组相比，我们观察到Aβ组在早期时间点由于AkaLumine的储备而显示出较低的生物发光强度，而在后期时间点由于AkaLumine的释放而显示出较高的强度。最后，我们证明了这种方法可以用于监测AD的进展和已经研究过的γ-分泌酶抑制剂avagacestat的治疗效果。重要的是，在测试的AD小鼠中，体内生物发光信号与Aβ的负担之间建立了良好的相关性（R2 = 0.81）。我们相信我们的方法可以轻松地应用于日常成像实验，并具有改变临床前AD研究日常实践的巨大潜力。

Bioluminescence imaging has changed the daily practice of preclinical research on cancer and other diseases over the last few decades; however, it has rarely been applied in preclinical research on Alzheimer's disease (AD). In this Article, we demonstrated that bioluminescence imaging could be used to report the levels of amyloid beta (Aβ) species in vivo. We hypothesized that AkaLumine, a newly discovered substrate for luciferase, could bind to Aβ aggregates and plaques. We further speculated that the Aβ aggregates/fibrils/plaques could be considered as "functional amyloids", which have a reservoir function to sequester and release AkaLumine to control the bioluminescence intensity, which could be used to report the levels of Aβs. Our hypotheses have been validated via in vitro solution tests, mimic studies with brain tissues and mice, two-photon imaging with AD mice, and in vivo bioluminescence imaging using transgenic AD mice that were virally transduced with AkaLuciferase (AkaLuc), a new luciferase that generates bioluminescence in the near-infrared window. As expected, compared to the control group, we observed that the Aβ group showed lower bioluminescence intensity due to AkaLumine sequestering at early time points, while higher intensity was due to AkaLumine releasing at later time points. Lastly, we demonstrated that this method could be used to monitor AD progression and the therapeutic effectiveness of avagacestat, a well-studied gamma-secretase inhibitor. Importantly, a good correlation (R2 = 0.81) was established between in vivo bioluminescence signals and Aβ burdens of the tested AD mice. We believe that our approach can be easily implemented into daily imaging experiments and has tremendous potential to change the daily practice of preclinical AD research.