| First Author | Alzghool OM | Year | 2021 |
| Journal | Neuropharmacology | Volume | 196 |
| Pages | 108676 | PubMed ID | 34216585 |
| Mgi Jnum | J:317307 | Mgi Id | MGI:6789805 |
| Doi | 10.1016/j.neuropharm.2021.108676 | Citation | Alzghool OM, et al. (2021) (S)-[(18)F]THK5117 brain uptake is associated with Abeta plaques and MAO-B enzyme in a mouse model of Alzheimer's disease. Neuropharmacology 196:108676 |
| abstractText | The mouse model of beta-amyloid (Abeta) deposition, APP/PS1-21, exhibits high brain uptake of the tau-tracer (S)-[(18)F]THK5117, although no neurofibrillary tangles are present in this mouse model. For this reason we investigated (S)-[(18)F]THK5117 off-target binding to Abeta plaques and MAO-B enzyme in APP/PS1-21 transgenic (TG) mouse model of Abeta deposition. APP/PS1-21 TG and wild-type (WT) control mice in four different age groups (2-26 months) were imaged antemortem by positron emission tomography with (S)-[(18)F]THK5117, and then brain autoradiography. Additional animals were used for immunohistochemical staining and MAO-B enzyme blocking study with deprenyl pre-treatment. Regional standardized uptake value ratios for the cerebellum revealed a significant temporal increase in (S)-[(18)F]THK5117 uptake in aged TG, but not WT, brain. Immunohistochemical staining revealed a similar increase in Abeta plaques but not endogenous hyper-phosphorylated tau or MAO-B enzyme, and ex vivo autography showed that uptake of (S)-[(18)F]THK5117 co-localized with the amyloid pathology. Deprenyl hydrochloride pre-treatment reduced the binding of (S)-[(18)F]THK5117 in the neocortex, hippocampus, and thalamus. This study's findings suggest that increased (S)-[(18)F]THK5117 binding in aging APP/PS1-21 TG mice is mainly due to increasing Abeta deposition, and to a lesser extent binding to MAO-B enzyme, but not hyper-phosphorylated tau. |
