Aims

In Alzheimer´s disease (AD), brain glucose hypometabolism, indexed by [¹⁸F]FDG-PET, is considered a biomarker of neurodegeneration. However, other brain cells, such as astrocytes and microglia, also consume considerable amounts of glucose and may contribute significantly to the [¹⁸F]FDG-PET signal in the brain. Thus, the cellular source of the [¹⁸F]FDG-PET signal remains controversial. Here, we aimed to evaluate whether canonical markers of different brain cell types (neuron, astrocyte, and microglia) associate with brain [¹⁸F]FDG-PET signal in a rat model of human amyloidosis.

Methods

[¹⁸F]FDG-PET imaging was conducted in ten-month-old APP/PS1 (TgF344-AD, n=8) and wild-type (WT, n=6) rats. Next, we evaluated the gene expression of GFAP, NeuN, and IBA1 in the frontal and temporoparietal cortices and cerebellum. GFAP protein levels were also quantified in the same brain regions, cerebrospinal fluid (CSF), and plasma. Association maps integrating protein or mRNA with brain [¹⁸F]FDG-PET were conducted at the voxel level using RMINC. Differences were considered statistically significant at p < 0.05 (t > 2).

Results

GFAP mRNA levels in the temporoparietal (local maxima, t₍₁₃₎=9.4; Fig1A) and frontal (local maxima, t₍₁₃₎= 6.6; Fig1A) cortices positively correlated with brain [¹⁸F]FDG-PET. No associations were found with neuronal and microglial markers mRNA levels (t₍₁₃₎<2; Fig1B and Fig1C, respectively). Furthermore, we found positive associations between plasma GFAP and brain [¹⁸F]FDG-PET signal (local maxima, t₍₁₃₎= 10.62; Fig1E), but not with CSF GFAP (t₍₁₃₎<2; Fig1F).

Conclusions

Our findings suggest that astrocyte markers are more closely associated with brain [¹⁸F]FDG-PET signal than neuronal and microglial markers.

Figure 1. Correlation between gene expression, protein immunocontent, fluid biomarkers and [¹⁸F]FDG-PET SUVr.