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

ABSTRACT Non‐motor symptoms in Parkinson's disease (PD) may be influenced by the α4β2* subtype of nicotinic acetylcholine receptors (nAChRs) present in the hippocampus (HP) and subiculum (SUB). To continue efforts in positron emission tomography (PET) diagnostics for PD, autoradiographic [ 18 F]nifene binding to α4β2* nAChR was quantitatively assessed in the HP–SUB of PD ( n = 27; 14 males and 13 females) and cognitively normal (CN) ( n = 32; 16 males and 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. The SUB had greater [ 18 F]nifene binding (51%–85%) compared to HP in all cases. Significantly higher [ 18 F]nifene binding (>250%; p < 0.0001) 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, whereas CN = 1.33, a >150% increase in PD ( p < 0.0001). Binding of [ 18 F]nifene to GM was >250% greater than WM in PD for both male and female. Male CN exhibited an increase, whereas male PD exhibited a significant decrease in [ 18 F]nifene binding with aging, whereas 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.