In-vivo quantification analysis of activated microglia in the brain of dementia

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As a maker for the early diagnosis of the dementia with PET, we developed the new radioactive ligand [^<11>C]DAA1106, which has high permeability to the brain and shows high affinity and specificity to the peripheral benzodiazepine receptor (PBR). In vitro and ex-vivo study using the model mouse of Alzheimer disease, we found the high density of PBR was localized in the activated microglia at surroundings of senile plaque of model mouse. The change of PBR in the brain of Alzheimer disease should reflect the activity of microglia related to the effect of senile plaque specific to neuronal degeneration in this disease.We examined whether we can diagnose the dementia in early stage by the quantification of the PBR with PET using [^<11>C]DAA1106 in in-vivo human study. We performed the PET scan with [^<11>C]DAA1106 on the group of patients of Alzheimer disease (n=10) and age-matched control group (n=11). Results showed significant increase of PBR-binding potential (BP) in the broad brain regions in the group of Alzheimer disease when compared to the age-matched control group. Further, to examine whether we can diagnose the dementia in very early stage before appearance of demented symptoms, we performed the scan on the subjects who had mild cognitive impairment (MCI), but cannot be diagnosed as the dementia at the time of PET scanning (n=7). We found the significant increase of PBR-BP in this group in broad brain regions when compared to the control group.In conclusion, it was shown that PET scan with [^<11>C]DAA1106 can show the increase of PBR which might be related to the neurodegenerative process in the Alzheimer disease. In most of the cases, MCI can be regarded as the pre-stage of dementia, and we can detect the abnormality of PBR-BP even before symptoms of dementia clearly appeared. PET scan with [^<11>C]DAA1106 should be useful method for the early diagnosis of the dementia and other neuronal degenerative diseases.