Postmortem binding studies have established that the concentration of a 4 b 2 -nicotinic acetylcholine receptors (a 4 b 2 -nAChR) is reduced in advanced Alzheimer disease (AD). However, the status of this receptor in mild or prodromal AD has remained the subject of controversy. Methods: We compared a 4 b 2 -nAChR availability in 8 brain regions of living human subjects who had AD and mild cognitive impairment (MCI) with that in age-matched healthy control subjects by using the ligand 123 I-5-IA-85380 ( 123 I-5-IA) and SPECT. All subjects (n 5 32) were nonsmokers; they were administered 123 I-5-IA as a bolus plus a constant infusion and imaged 6-8 h later under equilibrium conditions. The effect of diagnosis on regional a 4 b 2 -nAChR availability (regional brain activity/total parent concentration in plasma, proportional to the binding potential) was analyzed using multivariate analysis of covariance, controlling for the effects of age and sex. Results: Despite a significant overall effect of diagnostic group on mean a 4 b 2 -nAChR availability, univariate analyses revealed no group differences for any brain region analyzed. An exploratory analysis of the relationship between regional a 4 b 2 -nAChR availability and neuropsychologic variables yielded several plausible correlations. However, after Bonferroni adjustment, only the correlation between the anterior cingulate and the Trail Making Test, Part B, in the healthy control subjects remained significant. Conclusion: These results are consistent with several postmortem and in vivo studies suggesting the preservation of nAChRs during the prodromal and early stages of AD. They support the interpretation that nAChR and other cholinergic reductions in AD are late-stage phenomena.