Disruption of normal brain distribution of [18F]Nifene to α4β2* nicotinic acetylcholinergic receptors in old B6129SF2/J mice and transgenic 3xTg-AD mice model of Alzheimer's disease: In Vivo PET/CT imaging studies.

The 3xTg-AD transgenic mouse model develops Aβ plaque and tau pathology and is purported to closely resemble pathological development in the human Alzheimer's disease (AD) brain. Nicotinic acetylcholine receptors (nAChRs) α4β2* subtype, was studied in this mouse model using [18F]nifene PET/CT and compared with non-transgenic B6129SF2/J mice (male and female). Young 2-month old B6129SF2/J exhibited normal [18F]nifene distribution (measured as standard uptake volume ratios, SUVR with cerebellum as reference) thalamus (TH) 3.12> medial prefrontal cortex (mPFC) 2.33> frontal cortex (FC) 2.06> hippocampus-subiculum (HP-SUB) 1.6. At 11-months of age, B6129SF2/J exhibited high, irreversible and non-saturable [18F]nifene binding in mPFC higher than in TH (mPFC 3.8> TH 2.82> FC 1.79> HP-SUB 1.73). The 3xTg-AD also exhibited high mPFC binding, although the region of highest binding within the mPFC was different compared to B6129SF2/J mice (mPFC 2.44> TH 2.27> FC 1.61> HP-SUB 1.48). [125I]IBETA and immunohistochemistry in 3xTg-AD brain slices confirmed Aβ plaques. The TH of 3xTg-AD mice had lower [18F]nifene binding (reduced by approximately 20 %) compared to both, young and old B6129SF2/J, and was significant. The mPFC [18F]nifene binding was significantly higher in the old B6129SF2/J compared to both the young B6129SF2/J and the 3xTg-AD mice (>150 %). Overall, 3xTg-AD transgenic mice had reduced [18F]nifene binding compared to B6129SF2/J controls, suggesting possible effects of Aβ plaques and Tau on α4β2* nAChRs.