Multiphoton imaging in mouse models of Alzheimer's disease

摘要

Alzheimer's disease is characterized by the presence of neurofibrillary tangles and senile plaques in the brain. Clinical techniques are just becoming available for detecting plaques, allowing a definitive diagnosis of the disease. Using multiphoton microscopy and transgenic mouse models that develop senile plaques as they age, we have demonstrated chronic, in vivo imaging of these neuropathological lesions. We have used these tools to evaluate contrast agents with high affinity and specificity for senile plaques that would be suitable for non-invasive imaging with PET scanning if appropriately radiolabeled. These imaging tools should translate into early diagnostic procedures, as well as end-points for clinical trials aimed at clearing senile plaques from the brain. We have also developed FLIM for FRET determinations in vitro and in vivo between appropriate donor and acceptor fluorophores to examine the proximity of domains within a single protein. These results indicate that FRET measurements using FLIM can determine interactions of proteins on the nanometer scale, facilitating an understanding of both static and dynamic protein assemblies in neuropathological diseases.