Validation of mGluR5 as a imaging biomarker for Alzheimer's disease

초록

Background / Aims: Glutamate is the major excitatory neurotransmitter in central nervous system and it regulates learning and memory.1 Previous studies demonstrated that Aβ oligomers (Aβo) directly impose deleterious effects on glutamatergic neurotransmission, particularly on the metabotropic glutamate receptor type 5 (mGluR5).2 Dysregulation of mGluR5 by Aβo synaptic toxicity is known to be related with the early symptom of cognitive dysfunction in Alzheimer's disease (AD).3 The purpose of this research is to validate the potential of mGluR5 as a biomarker for AD by means of positron emission tomography. Methods: Four male 5xFAD transgenic mice as a rodent model of Alzehimer's disease and same number of wild type mice as agematched controls. The mice were anesthetized with 2.5% isoflurane in oxygen and [18F]FPEB was intraveinously administered. Simultaneously PET scan was performed for 90 min in the list mode. Volumes of interests (VOIs) are hippocampus, striatum, and cerebellum. Results: Brain PET imaging revealed that radioactivities in the mGluR5 rich regions such as hippocampus and striatum showed 18 - 21% lower uptakes in the 5xFAD group compared with control group. Also, non-displaceable binding values based on the cerebellum for 5xFAD were 22-25% lower than those for control group. Conclusion: mGluR5 levels in 5xFAD mice were down regulated in the limbic system. From this perspective, mGluR5 is considered as an effective imaging biomaker for AD.