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Abstract

This study aimed to investigate how amyloid pathology affects the functional aspects of neurotransmitter systems in Alzheimer’s disease. APPswe/PS2 mice (21 months of age) and wild-type (WT) mice underwent positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). First, we obtained 18F-FDG and 18F-florbetaben PET scans to evaluate neuronal integrity and amyloid pathology. Second, 18F-FPEB and 18F-FMZ PET data were acquired to assess the excitatory-inhibitory neurotransmission. Third, to monitor the dopamine system, 18F-fallypride PET was performed. Amyloid PET imaging revealed that radioactivity was higher in the AD group than that in the WT group, which was validated by immunohistochemistry. In the cortical and limbic areas, the AD group showed a 25–27% decrease and 14–35% increase in the glutamatergic and GABAergic systems, respectively. The dopaminergic system in the AD group exhibited a 29% decrease in brain uptake compared with that in the WT group. A reduction in glutamate, N-acetylaspartate, and taurine levels was observed in the AD group using MRS. Our results suggest that dysfunction of the neurotransmitter system is associated with AD pathology. Among the systems, the GABAergic system was prominent, implying that the inhibitory neurotransmission system may be the most vulnerable to AD pathology.

치매 쥐(APPswe/PS2, AD)와 정상쥐 (WT)에서 글루코스, 아밀로이드, 글루타메이트, 가바, 도파만계에 선택적으로 결합하는 방사성의약품을 주사한 후 양전자방출단층촬영술(PET)을 시행한 결과, 치매 쥐에서 억제성 신경전달체계인 가바계의 방사성의약품 섭취가 정상군보다 높았고, 흥분성 및 보상과 관련된 글루타메이트-도파민계는 정상군보다 낮은 뇌흡수를 보였습니다.

Se Jong Oh1,  Namhun Lee1,  Kyung Rok Nam1,  Kyung Jun Kang1,  Sang Jin Han1,  Kyo Chul Lee1,  Yong Jin Lee1 and  Jae Yong Choi1,2*