Calcium sensor Yellow Cameleon 3.6 as a tool to support the calcium hypothesis of Alzheimer's disease

INTRODUCTIONAlzheimer'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. METHODSHere 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. RESULTSYC3.6 studies showed that amyloidosis preceded dysfunction in neuronal calcium signaling and changes in synapse structure. This evidence supports the Calcium Hypothesis. DISCUSSIONIn vivo YC3.6 studies point to calcium signaling as a promising therapeutic target; however, additional work is necessary to translate these findings to humans.

Automated summary

Alzheimer's disease is a neurodegenerative disease associated with increasing cases of dementia, and its etiology is widely debated. The Calcium Hypothesis proposes that dysfunction in calcium signaling is the common pathway leading to neurodegeneration. Using YC3.6, studies have shown that amyloidosis precedes dysfunction in neuronal calcium signaling and changes in synapse structure, supporting the Calcium Hypothesis. However, further research is needed to translate these findings into human therapies.