Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts, USA.
Alzheimers Dement. 2023 Sep;19(9):4196-4203. doi: 10.1002/alz.13111. Epub 2023 May 8.
Alzheimer's disease (AD) is a neurodegenerative disease with increasing relevance as dementia cases rise. The etiology of AD is widely debated. The Calcium Hypothesis of Alzheimer's disease and brain aging states that the dysfunction of calcium signaling is the final common pathway leading to neurodegeneration. When the Calcium Hypothesis was originally coined, the technology did not exist to test it, but with the advent of Yellow Cameleon 3.6 (YC3.6) we are able to test its validity.
Here we review use of YC3.6 in studying Alzheimer's disease using mouse models and discuss whether these studies support or refute the Calcium Hypothesis.
YC3.6 studies showed that amyloidosis preceded dysfunction in neuronal calcium signaling and changes in synapse structure. This evidence supports the Calcium Hypothesis.
In vivo YC3.6 studies point to calcium signaling as a promising therapeutic target; however, additional work is necessary to translate these findings to humans.
阿尔茨海默病（AD）是一种神经退行性疾病，随着痴呆病例的增加，其相关性也越来越高。AD 的病因广泛存在争议。阿尔茨海默病和大脑老化的钙假说认为，钙信号功能障碍是导致神经退行性变的最终共同途径。当钙假说最初提出时，尚无技术可以对其进行检验，但随着 Yellow Cameleon 3.6（YC3.6）的出现，我们能够检验其有效性。
在这里，我们回顾了使用 YC3.6 研究阿尔茨海默病的小鼠模型，并讨论了这些研究是否支持或反驳钙假说。
YC3.6 的研究表明，淀粉样蛋白病变先于神经元钙信号功能障碍和突触结构变化。这一证据支持钙假说。
体内 YC3.6 的研究表明，钙信号是一个有前途的治疗靶点；然而，将这些发现转化为人类还需要做更多的工作。
