4 2 nicotinic receptor status in Alzheimer's disease using 123I-5IA-85380 single-photon-emission computed tomography

Background: Loss of the α4β2 nicotinic receptor subtype is found at autopsy in Alzheimer's disease. Objective: To investigate in vivo changes in this receptor using single-photon-emission CT (SPECT) with 123 I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380), a novel nicotinic acetylcholine receptor ligand which binds predominantly to the α4β2 receptor. Methods: 32 non-smoking subjects (16 with Alzheimer's disease and 16 normal elderly controls) underwent 123 I-5IA-85380 and perfusion (99m Tc-hexamethylenepropyleneamine oxime (HMPAO)) SPECT scanning. Region of interest analysis was performed with cerebellar normalisation. Results: Significant bilateral reductions in nicotinic receptor binding were identified in frontal (left, p = 0.004; right, p = 0.002), striatal (left, p = 0.004; right, p = 0.003), right medial temporal (p = 0.04) and pons (p