As a
neuromodulator, the
neurotransmitter acetylcholine plays an important role in cognitive, mood, locomotor, sleep/wake, and olfactory functions. In the pathophysiology of most
neurodegenerative diseases, such as
Alzheimer disease (AD) or Lewy body disorder (LBD),
cholinergic receptors, transporters, or
enzymes are involved and relevant as imaging targets. The aim of this review is to summarize current knowledge on PET imaging of
cholinergic neurotransmission in
neurodegenerative diseases. For PET imaging of presynaptic
vesicular acetylcholine transporters (VAChT), (-)-18F-fluoroethoxybenzovesamicol (18F-FEOBV) was the first PET
ligand that could be successfully translated to clinical application. Since then, the number of 18F-FEOBV PET investigations on patients with AD or LBD has grown rapidly and provided novel, important findings concerning the pathophysiology of AD and LBD. Regarding the α4β2
nicotinic acetylcholine receptors (nAChRs), various second-generation PET
ligands, such as
18F-nifene,
18F-AZAN, 18F-XTRA, (-)-18F-flubatine, and (+)-18F-
flubatine, were developed and successfully translated to human application. In
neurodegenerative diseases such as AD and LBD, PET imaging of α4β2 nAChRs is of special value for monitoring
disease progression and drugs directed to α4β2 nAChRs. For PET of α7 nAChR,
18F-ASEM and 11C-MeQAA were successfully applied in
mild cognitive impairment and AD, respectively. The highest potential for α7 nAChR PET is seen in staging, in evaluating
disease progression, and in
therapy monitoring. PET of selective
muscarinic acetylcholine receptors (mAChRs) is still in an early stage, as the development of subtype-selective radioligands is complicated. Promising radioligands to image mAChR subtypes M1 (11C-LSN3172176), M2 (18F-FP-TZTP), and M4 (11C-MK-6884) were developed and successfully translated to humans. PET imaging of mAChRs is relevant for the assessment and monitoring of
therapies in AD and LBD. PET of
acetylcholine esterase activity has been investigated since the 1990s. Many PET studies with 11C-PMP and 11C-MP4A demonstrated cortical
cholinergic dysfunction in
dementia associated with AD and LBD. Recent studies indicated a solid relationship between subcortical and cortical
cholinergic dysfunction and noncognitive dysfunctions such as balance and gait in LBD. Taken together, PET of distinct components of
cholinergic neurotransmission is of great interest for diagnosis, disease monitoring, and
therapy monitoring and to gain insight into the pathophysiology of different
neurodegenerative disorders.