GABA transporters gene expression associates with [18F]FDG‐PET signal in regions typically hypometabolic in Alzheimer’s disease

Abstract

AbstractBackgroundIt is suggested that the [18F]fluorodeoxyglucose(FDG)‐PET signal reflects astrocyte and neuronal activity, with the excitatory glutamate uptake by astrocytes as the trigger for brain glucose metabolism. The inhibitory neurotransmitter γ‐aminobutyric acid (GABA) is taken up by neurons and astrocytes through the GABA transporters (GAT) 1 and 3. However, its role in the [18F]FDG‐PET signal in healthy aging and Alzheimer’s disease (AD) remains poorly investigated. Thus, we aimed to explore associations between neuronal and astrocytic GABA transporters gene expression with [18F]FDG‐PET in cognitively unimpaired (CU) and AD individuals.MethodWe obtained [18F]FDG‐PET imaging data of CU and AD from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (Table 1). GAT1 and GAT3 gene expression in the brain was obtained from the Allen Brain Atlas (Table 1, Figure 1). We extracted SUVr (pons as reference region) and mRNA values using the RMINC package and performed Pearson’s correlation to test the association between [18F]FDG‐PET and GABA transporters mRNA (p‐value < 0.05).ResultIn brain regions typically hypometabolic in AD, we observed a strong positive association of [18F]FDG‐PET SUVr with GAT1 and GAT3 gene expression in CU (GAT1: r = 0.93; p < 0.0001; Figure 2A, GAT3: r = 0.94; p < 0.0001; Figure 2B) and AD individuals (GAT1: r = 0.9; p < 0.0001; Figure 2A, GAT3: r = 0.92; p < 0.0001; Figure 2B). By contrast, in brain regions typically resilient, we found a weak correlation with CU individuals (GAT1: r = 0.32; p = 0.016; Figure 2C, GAT3: r = 0.26; p = 0.04; Figure 2D) and no significant correlation in AD patients (GAT1: r = 0.24; p = 0.07; Figure 2C, GAT3: r = 0.24; p = 0.059; Figure 2D).ConclusionOur results demonstrate a significant strong positive association between [18F]FDG‐PET SUVr and GABA transporters gene expression in CU and AD in hypometabolic regions. These findings suggest that GABA transporters are involved with brain glucose metabolism in regions classically vulnerable to AD pathology.