Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Nat Biomed Eng. 2023 Mar;7(3):270-280. doi: 10.1038/s41551-023-01003-7. Epub 2023 Feb 6.
Non-invasive methods for the in vivo detection of hallmarks of Alzheimer's disease can facilitate the study of the progression of the disease in mouse models and may enable its earlier diagnosis in humans. Here we show that the zwitterionic heptamethine fluorophore ZW800-1C, which has peak excitation and emission wavelengths in the near-infrared optical window, binds in vivo and at high contrast to amyloid-β deposits and to neurofibrillary tangles, and allows for the microscopic imaging of amyloid-β and tau aggregates through the intact skull of mice. In transgenic mouse models of Alzheimer's disease, we compare the performance of ZW800-1C with that of the two spectrally similar heptamethine fluorophores ZW800-1A and indocyanine green, and show that ZW800-1C undergoes a longer fluorescence-lifetime shift when bound to amyloid-β and tau aggregates than when circulating in blood vessels. ZW800-1C may prove advantageous for tracking the proteinic aggregates in rodent models of amyloid-β and tau pathologies.
非侵入性方法可用于体内检测阿尔茨海默病的标志性特征，这有助于研究小鼠模型中疾病的进展，也可能使人类更早地诊断出这种疾病。在这里，我们展示了具有近红外光学窗口中激发和发射峰的两性离子七甲川荧光染料 ZW800-1C 能够在体内与淀粉样β沉积物和神经原纤维缠结高对比度结合，并允许通过完整的小鼠颅骨对淀粉样β和 tau 聚集体进行微观成像。在阿尔茨海默病的转基因小鼠模型中，我们比较了 ZW800-1C 与两种光谱相似的七甲川荧光染料 ZW800-1A 和吲哚菁绿的性能，并表明 ZW800-1C 与淀粉样β和 tau 聚集体结合时的荧光寿命变化比在血管中循环时更长。ZW800-1C 可能在跟踪淀粉样β和 tau 病理学的啮齿动物模型中的蛋白聚集体方面具有优势。
