Opening a window on cerebral cholinergic function

Just over two decades ago, PET emerged from the laboratory as a result of advances in radiochemical synthesis, detector physics, and image reconstruction techniques. The initial use of PET in neurology predominantly involved studies of cerebral blood flow (CBF) and glucose metabolism to define functional abnormalities in disease and map normal cognitive processes. Yet one of the greatest potential strengths of PET imaging is the ability to measure substances in the brain that occur in nanomolar concentrations, such as neurotransmitters and their receptors. A particularly good example of PET neurotransmitter system imaging is the use of [¹⁸F]-fluorodopa and related compounds to study PD. Such work has resulted in important insights into the natural history and differential diagnosis of PD, its early detection, and development and monitoring of therapy.1,2 In this issue of Neurology, Kuhl et al.3 provide new data on a PET tracer for the quantitative imaging of brain acetylcholinesterase (AChE) activity, illustrating an analogous use of PET to study the cholinergic system in aging and AD.

The importance of acetylcholine in normal memory function has been appreciated for years, as has the fact that depletion of acetylcholine is the primary neurochemical abnormality in AD. To date, brain acetylcholine measurements in AD have been performed postmortem. Although this method has been sufficient to demonstrate the importance of the cholinergic deficit in AD and, indeed, produced the data that led to the first neurochemically specific and efficacious therapy for AD, it has obvious limitations. For this reason, several laboratories have been investigating PET radiotracer methods for studying the cholinergic system in patients. Three general approaches have been used: 1) presynaptic terminals have been studied with derivatives of vesamicol to label the vesicular …