Parkinson’s disease (PD)
Parkinson’s disease is a progressive neurodegenerative movement disorder, characterized by motor symptoms, but causing also various non-motor symptoms. Motor symptoms include bradykinesia (slowness of movement), tremor, and rigidity (parkinsonism syndrome). Non-motor symptoms, related to the pathophysiology of PD, include depression, pain, anxiety, dementia, and fatigue.
Dopaminergic degeneration is an age-related process, but in PD the loss of dopaminergic neurons in the substantia nigra is much faster than in normal ageing. Parkinsonism is usually caused by idiopathic PD, but can be seen in patients without dopaminergic deficit, and is prevalent in disorders such as progressive supranuclear palsy, multiple system atrophy, and microvascular disease. Lesion network mapping suggests that claustrum has a central role in parkinsonism (Joutsa et al., 2018).
Presynaptic dopaminergic neurons can be studied with dopamine transporter (DAT) binding PET tracers, including [11C]PE2I, [11C]CFT and [18F]FP-CIT; the activity of aromatic amino acid decarboxylase (AADC) using 6-[18F]-L-DOPA (FDOPA); or vesicular monoamine transporter type 2 (VMAT2). Imaging studies of presynaptic striatal dopaminergic function show clear differences patient groups with Parkinson’s disease or atypical parkinsonisms (Kaasinen et al., 2019). Postsynaptic (dopamine receptors can be targeted by many PET tracers. This allows the detection of possible upregulation in the early phase of PD, and also to assess changes in synaptic dopamine concentration.
Serotonergic system is impaired in PD, and several serotonin system targeting PET tracers have been used in studies of motor and non-motor symptoms of PD.
Cholinergic neurotransmission is decreased in PD. AChE, mAChR, and nAChR tracers have been used in PET studies of PD.
Neuroinflammatory processes are involved in development of PD, and TSPO radioligands are used to study microglial activation in PD. Mitochondrial dysfunction and oxidative stress induced apoptotic processes are central to neurodegenerative diseases, including PD and Alzheimer’s disease. Mitochondria are main producers of reactive oxygen species (ROS), but also auto-oxidation of dopamine leads to ROS formation.
PD is neuropathologically characterized by intracellular misfolded α-synuclein-rich inclusions (Lewy bodies). In addition, extracellular deposits of amyloid-β and intraneuronal deposits of tau protein as neurofibrillary tangles are found in PD patients.
PD can be discriminated from atypical parkinsonism based on serum neurofilament light chain (Marquez et al., 2019).
Barber TR, Klein JC, Mackay CE, Hu MTM. Neuroimaging in pre-motor Parkinson’s disease. Neuroimage Clin. 2017; 15:215-227. doi: 10.1016/j.nicl.2017.04.011.
Bhatia K, Chaudhuri KR, Stamelou M (eds.): Parkinson’s Disease. Int Rev Neurobiol 132, Academic Press, 2017. ISBN: 9780128098509.
Buhlman LM (ed.): Mitochondrial Mechanisms of Degeneration and Repair in Parkinson’s Disease. Springer, 2016. doi: 10.1007/978-3-319-42139-1.
Hirao K, Pontone GM, Smith GS. Molecular imaging of neuropsychiatric symptoms in Alzheimer’s and Parkinson’s disease. Neurosci Biobehav Rev. 2015; 49: 157-170. doi: 10.1016/j.neubiorev.2014.11.010.
Järvelä JT, Rinne JO, Eskola O, Kaasinen V. Mortality in Parkinson’s disease is not associated with the severity of early dopaminergic defect. Parkinsonism Relat Disord. 2014; 20(8): 894-897. doi: 10.1016/j.parkreldis.2014.05.010.
Meles SK, Teune LK, de Jong BM, Dierckx RA, Leenders KL. Metabolic imaging in Parkinson disease. J Nucl Med. 2017; 58(1): 23-28. doi: 10.2967/jnumed.116.183152.
Minagar A (ed.): Neuroinflammation. Elsevier, 2011. ISBN 978-0-12-384913-7.
Misu Y, Goshima Y (eds.): Neurobiology of DOPA as a Neurotransmitter. CRC Taylor & Francis, 2006. ISBN: 978-0-415-33291-0.
Niccolini F, Politis M. A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism. Eur J Nucl Med Mol Imaging 2016; 43: 2244-2254. doi: 10.1007/s00259-016-3464-8.
Strafella AP, Bohnen NI, Perlmutter JS, et al. Molecular imaging to track Parkinson’s disease and atypical parkinsonisms: New imaging frontiers. Mov Disord. 2017; 32(2): 181-192. doi: 10.1002/mds.26907.
Verstreken P (ed.): Parkinson’s Disease - Molecular Mechanisms Underlying Pathology. Academic Press, 2017. ISBN: 978-0-12-803783-6.
Updated at: 2019-05-12
Created at: 2017-11-16
Written by: Vesa Oikonen