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Development of CNS imaging using the radioactive acetylcholine analog method in the mid-1990s opened a window on cerebral cholinergic function in vivo.1 Two PET tracers, [11C]MP4A and its sister compound [11C]PMP (or [11C]MP4P), are currently used in vivo for measurement of brain acetylcholinesterase (AChE) activity in humans. Both radiotracers readily pass through the blood–brain barrier following IV injection and are hydrolyzed by AChE localized within the intersynaptic space, predominantly on presynaptic cholinergic neurons. Subsequently, radiolabeled metabolites are trapped locally in the brain according to the distribution of enzyme activity.
PET studies using these radiotracers have revealed reduction of cerebral cortical AChE activity in Alzheimer disease (AD)2 and Parkinson disease (PD),3,4 as well as more severe reduction of cortical AChE activity in PD with dementia (PDD)4 and dementia with Lewy bodies (DLB),4 which suggests loss of ascending cholinergic projections from the basal forebrain. Reduction of cortical AChE activity is correlated in turn with cognitive dysfunction in AD,2 PD, and PDD/DLB,4 indicating that the loss of the ascending cholinergic system from the basal forebrain plays a pivotal …
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