Cognitive Function and Calcium. Molecular neuroimaging and calcium

Neurodegenerative dementias exemplified by Alzheimer's disease are neuropathologically characterized by deposition of protein aggregates such as amyloid β peptide (Aβ), tau protein. Aβ is known to act as a scaffold to promote clustering of metabotropic glutamate receptor type 5 (mGluR5) at the synaptic compartment, and tau is also supposed to mediate phosphorylation of N-methyl-D-aspartate (NMDA) receptor at the excitatory postsynapse. These pathologic changes reinforce coupling of mGluR5 and NMDA receptor, and induce influx of calcium into dendritic spines. Synaptic clustering of mGluR5 and altered coupling of mGluR5 and NMDA receptor can be visualized in living brains using positron emission tomography (PET) and a radioligand for mGluR5, and this technology could offer a biomarker reflecting disruption of intraneuronal calcium homeostasis. Potential drugs targeting mGluR5 and NMDA receptor would exert therapeutic efficacies against dementing illnesses in a manner dependent on pathogenetic stages, and PET imaging of mGluR5 and related components would help to determine an optimal time point to initiate treatment with each drug on a personalized basis.