Mapping the Silent Onset of Parkinson’s Disease: Monoamine Imaging in the Era of the Race for Preclinical Intervention

Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov disorders: official J Mov Disorder Soc. 2015;30(12):1591–601. https://doi.org/10.1002/mds.26424.

Article  Google Scholar 

Virameteekul S, Revesz T, Jaunmuktane Z, Warner TT, De Pablo-Fernández E. Clinical Diagnostic Accuracy of Parkinson’s Disease: Where Do We Stand? Movement disorders: official. J Mov Disorder Soc. 2023;38(4):558–66. https://doi.org/10.1002/mds.29317.

Article  Google Scholar 

Simuni T, Chahine LM, Poston K, Brumm M, Buracchio T, Campbell M, et al. A biological definition of neuronal α-synuclein disease: towards an integrated staging system for research. Lancet Neurol. 2024;23(2):178–90. https://doi.org/10.1016/s1474-4422(23)00405-2.

Article  CAS  PubMed  Google Scholar 

Höglinger GU, Adler CH, Berg D, Klein C, Outeiro TF, Poewe W, et al. A biological classification of Parkinson’s disease: the SynNeurGe research diagnostic criteria. Lancet Neurol. 2024;23(2):191–204. https://doi.org/10.1016/s1474-4422(23)00404-0.

Article  CAS  PubMed  Google Scholar 

Son HJ, Oh JS, Oh M, Lee SJ, Oh SJ, Chung SJ, et al. Test-retest reproducibility of dopamine transporter density measured with [(18)F]FP-CIT PET in patients with essential tremor and Parkinson’s disease. Ann Nucl Med. 2021;35(3):299–306. https://doi.org/10.1007/s12149-020-01561-9.

Article  CAS  PubMed  Google Scholar 

Horsager J, Andersen KB, Knudsen K, Skjærbæk C, Fedorova TD, Okkels N, et al. Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study. Brain. 2020;143(10):3077–88. https://doi.org/10.1093/brain/awaa238.

Article  PubMed  Google Scholar 

Andersen KB, Krishnamurthy A, Just MK, Van Den Berge N, Skjærbæk C, Horsager J, et al. Sympathetic and parasympathetic subtypes of body-first Lewy body disease observed in postmortem tissue from prediagnostic individuals. Nat Neurosci. 2025;28(5):925–36. https://doi.org/10.1038/s41593-025-01910-9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cilia R, Arnaldi D, Ballanger B, Ceravolo R, De Micco R, Del Sole A, et al. Neuroimaging and Pathology Biomarkers in Parkinson’s Disease and Parkinsonism. Brain Sci. 2026;16(1). https://doi.org/10.3390/brainsci16010110.

Kaasinen V, Vahlberg T. Striatal dopamine in Parkinson disease: A meta-analysis of imaging studies. Ann Neurol. 2017;82(6):873–82. https://doi.org/10.1002/ana.25103.

Article  CAS  PubMed  Google Scholar 

Pudis M, Rodríguez-Bel L, Cortés-Romera M, Suárez-Piñera M. Dopaminergic Pathway Imaging. Neurol Clin Pract. 2026;16(2):e200599. https://doi.org/10.1212/CPJ.0000000000200599.

Article  Google Scholar 

Wallert ED, van de Giessen E, Knol RJJ, Beudel M, de Bie RMA, Booij J. Imaging Dopaminergic Neurotransmission in Neurodegenerative Disorders. J Nucl Med. 2022;63(Suppl 1):s27–32. https://doi.org/10.2967/jnumed.121.263197.

Article  CAS  Google Scholar 

Dhadamus M, Delva A, Deckers W, Vandenberghe W, Van Laere K. Normal [(18)F]FE-PE2I PET in Patients with Persistent Diagnostic Uncertainty after Abnormal [(123)I]FP-CIT SPECT. Mov disorders: official J Mov Disorder Soc. 2025;40(8):1709–13. https://doi.org/10.1002/mds.30255.

Article  Google Scholar 

Saari L, Kivinen K, Gardberg M, Joutsa J, Noponen T, Kaasinen V. Dopamine transporter imaging does not predict the number of nigral neurons in Parkinson disease. Neurology. 2017;88(15):1461–7. https://doi.org/10.1212/wnl.0000000000003810.

Article  CAS  PubMed  Google Scholar 

Honkanen EA, Saari L, Orte K, Gardberg M, Noponen T, Joutsa J, et al. No link between striatal dopaminergic axons and dopamine transporter imaging in Parkinson’s disease. Mov disorders: official J Mov Disorder Soc. 2019;34(10):1562–6. https://doi.org/10.1002/mds.27777.

Article  CAS  Google Scholar 

Kordower JH, Olanow CW, Dodiya HB, Chu Y, Beach TG, Adler CH, et al. Disease duration and the integrity of the nigrostriatal system in Parkinson’s disease. Brain. 2013;136(Pt 8):2419–31. https://doi.org/10.1093/brain/awt192.

Article  PubMed  PubMed Central  Google Scholar 

Arnaldi D, Mattioli P, Famà F, Girtler N, Brugnolo A, Pardini M, et al. Stratification Tools for Disease-Modifying Trials in Prodromal Synucleinopathy. Mov disorders: official J Mov Disorder Soc. 2022;37(1):52–61. https://doi.org/10.1002/mds.28785.

Article  Google Scholar 

Postuma RB, Iranzo A, Hu M, Högl B, Boeve BF, Manni R, et al. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain. 2019;142(3):744–59. https://doi.org/10.1093/brain/awz030.

Article  PubMed  PubMed Central  Google Scholar 

Brown EG, Chahine LM, Siderowf A, Gochanour C, Kurth R, Marshall MJ, et al. Staged Screening Identifies People with Biomarkers Related to Neuronal Alpha-Synuclein Disease. Ann Neurol. 2025;97(4):730–40. https://doi.org/10.1002/ana.27158.

Article  CAS  PubMed  Google Scholar 

Chahine L, Rosso AL, Troidl I, Ganguli M, Newman AB, Lopresti BJ, et al. Features of Prodromal Parkinson Disease and Dopaminergic Neurotransmission in Community-Dwelling Older Adults. Neurology. 2025;105(6):e214037. https://doi.org/10.1212/wnl.0000000000214037.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lindenbach D, Bishop C. Critical involvement of the motor cortex in the pathophysiology and treatment of Parkinson’s disease. Neurosci Biobehav Rev. 2013;37(10 Pt 2):2737–50. https://doi.org/10.1016/j.neubiorev.2013.09.008.

Article  PubMed  PubMed Central  Google Scholar 

Biondetti E, Santin MD, Valabrègue R, Mangone G, Gaurav R, Pyatigorskaya N, et al. The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson’s disease. Brain. 2021;144(10):3114–25. https://doi.org/10.1093/brain/awab191.

Article  PubMed  PubMed Central  Google Scholar 

Pyatigorskaya N, Magnin B, Mongin M, Yahia-Cherif L, Valabregue R, Arnaldi D, et al. Comparative Study of MRI Biomarkers in the Substantia Nigra to Discriminate Idiopathic Parkinson Disease. AJNR Am J Neuroradiol. 2018;39(8):1460–7. https://doi.org/10.3174/ajnr.A5702.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Biondetti E, Gaurav R, Yahia-Cherif L, Mangone G, Pyatigorskaya N, Valabrègue R, et al. Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson’s disease. Brain. 2020;143(9):2757–70. https://doi.org/10.1093/brain/awaa216.

Article  PubMed  Google Scholar 

Alushaj E, Handfield-Jones N, Kuurstra A, Morava A, Menon RS, Owen AM, et al. Increased iron in the substantia nigra pars compacta identifies patients with early Parkinson’sdisease: A 3T and 7T MRI study. Neuroimage Clin. 2024;41:103577. https://doi.org/10.1016/j.nicl.2024.103577.

Article  PubMed  PubMed Central  Google Scholar 

Bergsland N, Zivadinov R, Schweser F, Hagemeier J, Lichter D, Guttuso T. Jr. Ventral posterior substantia nigra iron increases over 3 years in Parkinson’s disease. Mov disorders: official J Mov Disorder Soc. 2019;34(7):1006–13. https://doi.org/10.1002/mds.27730.

Article  CAS  Google Scholar 

Brammerloh M, Morawski M, Friedrich I, Reinert T, Lange C, Pelicon P, et al. Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry. NeuroImage. 2021;239:118255. https://doi.org/10.1016/j.neuroimage.2021.118255.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schwarz ST, Afzal M, Morgan PS, Bajaj N, Gowland PA, Auer DP. The ‘swallow tail’ appearance of the healthy nigrosome - a new accurate test of Parkinson’s disease: a case-control and retrospective cross-sectional MRI study at 3T. PLoS ONE. 2014;9(4):e93814. https://doi.org/10.1371/journal.pone.0093814.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chougar L, Arsovic E, Gaurav R, Biondetti E, Faucher A, Valabrègue R, et al. Regional Selectivity of Neuromelanin Changes in the Substantia Nigra in Atypical Parkinsonism. Mov disorders: official J Mov Disorder Soc. 2022;37(6):1245–55. https://doi.org/10.1002/mds.28988.

Article  CAS  Google Scholar 

Palermo G, Francesconi A, Bellini G, Morganti R, Migaleddu G, Di Carlo DT, et al. Involvement of the Nigrostriatal Pathway in Patients With Idiopathic Normal Pressure Hydrocephalus and Parkinsonism. Neurology. 2025;104(5):e213352. https://doi.org/10.1212/wnl.0000000000213352.

Article  PubMed  Google Scho

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