Abstract
Nicotinic acetylcholinergic receptors (nAChRs), including the α4β2* subtype are involved in cognition, learning and memory and may be adversely affected in Alzheimer's disease (AD). In our efforts to consider translational use of [(18)F]nifene PET in AD, we report quantitative autoradiographic evaluation of α4β2* nAChRs using hippocampus-subiculum (HP-SUB) from cognitively normal (CN) and AD subjects. Brain slices were incubated in [(18)F]nifene for α4β2* nAChRs and adjacent sections were tested with [(18)F]flotaza for Aβ plaques and [(125)I]IPPI for tau. Anti-Aβ and anti-tau immunostaining were carried out on adjacent slices. Regions of interest were drawn and binding of [(18)F]nifene, [(18)F]flotaza and [(125)I]IPPI were quantified.All CN subjects exhibited significant [(18)F]nifene binding in the HP-SUB regions. Average [(18)F]nifene ratios of SUB to HP was 1.9, suggesting higher α4β2* nAChRs in the SUB versus HP regions. [(18)F]nifene binding did not change with aging in the female subjects, while the male subjects exhibited a weak positive correlation. There was a significant decrease in the binding of [(18)F]nifene in AD subjects compared to CN. Braak stage comparisons showed a decrease of [(18)F]nifene in stages V and VI, while [(18)F]flotaza and [(125)I]IPPI increased significantly. A negative correlation was observed between [(18)F]nifene vs [(18)F]flotaza and [(18)F]nifene vs [(125)I]IPPI across Braak stages I-VI. These findings suggest that α4β2* nAChR availability was effectively measured by [(18)F]nifene in the HP-SUB and was adversely affected by the presence of Aβ plaques and tau.