Multi-target PET evaluation in APP/PS1/tau mouse model of Alzheimer's disease

Positron emission tomography (PET) has great benefits for developing therapeutics and quantifying pathological markers in neuropsychiatric disorders. This study aimed to firstly demonstrate the feasibility of PET imaging for glucagon-like peptide-1 receptor (GLP-1R) in Alzheimer's disease (AD) and evaluate the GLP-1R expression. Besides, microglial activation, dopamine D2 receptor (D2R) expression, and glucose metabolism in the brain of APP/PS1/tau transgenic model of AD (3×Tg-AD) were also investigated by PET. [¹⁸F]FBEM-Cys³⁹-exendin-4, [¹⁸F]DPA-714, [¹⁸F]fallypride, and [¹⁸F]FDG were prepared and PET imaging acquisitions for 3×Tg-AD mice and wild-type (WT) mice were performed at 15, 30, and 60 min post-injection. Fifteen regions of interest (ROIs) were selected and %ID/g was calculated. The results showed that the uptake of [¹⁸F]FBEM-Cys³⁹-exendin-4 in 10 ROIs of 3×Tg-AD mice at 60 min post-injection was significantly lower than that of WT mice (p < 0.05). Besides, 3×Tg-AD mice showed significantly higher [¹⁸F]DPA-714 uptake in 7 ROIs and lower [¹⁸F]fallypride uptake in 4 ROIs compared to WT mice. [¹⁸F]FDG PET showed no significant differences in any ROIs between the two groups. A positive correlation between the uptake of [¹⁸F]fallypride and [¹⁸F]FBEM-Cys³⁹-exendin-4 could be found in the whole brain. In summary, these results validated the feasibility of GLP-1R PET in AD and demonstrated the reduced GLP-1R and D2R expression as well as increased microglial activation caused by AD.