Increased Binding of [ ¹⁸ F]Nifene, a PET Imaging Probe for α4β2* Nicotinic Acetylcholinergic Receptors in Hippocampus-Subiculum of Postmortem Human Parkinson’s Disease Brain

Non-motor symptoms in Parkinson’s disease (PD) may be influenced by the α4β2* subtype of nicotinic acetylcholine receptors (nAChR) present in the hippocampus and subiculum. To continue efforts in PET diagnostics for PD, autoradiographic [ ¹⁸ F]nifene binding to α4β2* nAChR was quantitively assessed in the hippocampus-subiculum (HP-SUB) of PD (n = 27; 14 males, 13 females) and cognitively normal (CN) (n = 32; 16 males, 16 females) cases. Anti-ubiquitin for Lewy body and anti-α-synuclein immunostaining on adjacent slices were analyzed in QuPath and [ ¹⁸ F]nifene binding was quantified in OptiQuant. Subiculum had greater [ ¹⁸ F]nifene binding (51% to 85%) compared to HP in all subjects. Significantly higher [ ¹⁸ F]nifene binding (>250%) was seen in PD SUB and PD HP compared to CN in both males and females. The grey matter (GM) to white matter (WM) ratio in PD=3.53 while CN=1.33, a >150% increase in PD. Binding of [ ¹⁸ F]nifene to GM and WM individually was >250% greater in PD compared to CN. Male CN exhibited an increase while and male PD exhibited a significant decrease in [ ¹⁸ F]nifene binding with aging, while females did not exhibit significant differences. In summary, α4β2* nAChR measured by [ ¹⁸ F]nifene is significantly upregulated in the PD HP and SUB. This increased [ ¹⁸ F]nifene binding may be of diagnostic value using PET imaging.