368. Muscarinic 2 receptors in cognitively normal young and old volunteers

Abstract

Decreases in nicotinic and muscarinic type 2 (M2) receptors have been noted, at autopsy, in Alzheimer’s Disease, and this decrease correlates with decreases in choline acetyltransferase (1). This suggests that M2 receptors are presynaptic autoreceptors and that their decrease is related to the loss of acetylcholine neurons (1). Most radiotracers developed for muscarinic receptors either have inadequate subtype selectivity or do not easily cross the blood brain barrier. The PET Department at NIH recently developed a tracer that binds to M2 receptors in the brain (2). With the idea that there is selective vulnerability of M2 receptors in Alzheimer’s disease, we are using this tracer to evaluate whether it binds to M2 receptors in humans, cortical and subcortical distribution of receptors, and whether there are differences in binding between different subject populations. Currently, we have used this tracer in 8 younger subjects and 14 older subjects and this data is being analyzed. Our hypotheses are that binding will be seen throughout the cortex with the highest areas of concentration in medial temporal and hippocampal regions and that there will be decreases in receptor density with aging. Future studies will include “at risk” and subjects treated with cholinergic medications to examine markers for drug responsiveness.