Comparing 7 nicotinic acetylcholine receptor binding, amyloid- deposition, and mitochondria complex-I function in living brain: A PET study in aged monkeys

摘要

This study was aimed to assess the correlations among 7 nicotinic acetylcholine receptor (7-nAChR) binding, amyloid- (A) deposition, and mitochondrial complex I (MC-I) activity in the brain of aged monkeys (Macaca mulatta). Positron emission tomography (PET) measurements with [C-11](R)-MeQAA, [C-11]PIB, and [F-18]BCPP-EF were conducted in monkeys in a conscious condition. [C-11](R)-MeQAA binding was analyzed by a simplified reference tissue model to calculate nondisplaceable binding potential (BPND), [C-11]PIB uptake was calculated by standard uptake value ratio (SUVR), and [F-18]BCPP-EF binding was determined by Logan graphical analysis to calculate total distribution volume (V-T) with arterial blood sampling. Higher brain uptake was determined in the thalamus, hippocampus, striatum, and cortical regions for [C-11](R)-MeQAA, while being lower in the cerebellum. Significant age-related reduction of [C-11](R)-MeQAA binding to 7-nAChR was determined only in the occipital cortex. The plot of Vt of [F-18]BCPP-EF against BPND of [C-11](R)-MeQAA indicated a significant negative correlation in the hippocampus and cortical regions in aged animals. Plotting of SUVR of [C-11]PIB against BPND of [C-11](R)-MeQAA showed a positive correlation. The in vivo binding of [C-11](R)-MeQAA could reflect the upregulation of 7-nAChR induced by neurodegenerative damage determined by A deposition as well as impaired MC-I activity in living brain. Synapse 69:475-483, 2015. (c) 2015 Wiley Periodicals, Inc.