Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Genetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Alzheimers Dement. 2021 Dec;17(12):1988-1997. doi: 10.1002/alz.12344. Epub 2021 Apr 15.
Aging is an inevitable physiological process and the biggest risk factor of Alzheimer's disease (AD). Developing an imaging tracer to visualize aging-related changes in the brain may provide a useful biomarker in elucidating neuroanatomical mechanisms of AD.
We developed and characterized a new tracer that can be used to visualize SIRT1 in brains related to aging and AD by positron emission tomography imaging.
The SIRT1 tracer displayed desirable brain uptake and selectivity, as well as stable metabolism and proper kinetics and distribution in rodent and nonhuman primate brains. This new tracer was further validated by visualizing SIRT1 in brains of AD transgenic mice, compared to nontransgenic animals.
Our SIRT1 tracer not only enables, for the first time, the demonstration of SIRT1 in animal brains, but also allows visualization and recapitulation of AD-related SIRT1 neuropathological changes in animal brains.
衰老是一个不可避免的生理过程，也是阿尔茨海默病（AD）的最大风险因素。开发一种可用于可视化大脑与衰老相关变化的成像示踪剂，可能为阐明 AD 的神经解剖机制提供一个有用的生物标志物。
我们开发并表征了一种新的示踪剂，通过正电子发射断层扫描成像，可以用于可视化与衰老和 AD 相关的 SIRT1。
SIRT1 示踪剂在啮齿动物和非人类灵长类动物的大脑中具有理想的脑摄取和选择性，以及稳定的代谢和适当的动力学和分布。通过与非转基因动物相比，在 AD 转基因小鼠的大脑中观察到该新示踪剂，验证了 SIRT1 的存在。
我们的 SIRT1 示踪剂不仅首次能够在动物大脑中显示 SIRT1，还能够可视化和再现动物大脑中与 AD 相关的 SIRT1 神经病理学变化。
