Parkinson disease is the second-most common neurodegenerative disorder that affects 2–3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.
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The authors are grateful to U. Zijerveld for providing administrative support.
W.P. reports personal fees from AbbVie, Allergan, AstraZeneca, BIAL, Boehringer-Ingelheim, Boston Scientific, GlaxoSmithKline, Ipsen, Lundbeck, Medtronic, MSD, Merck-Serono, Merz Pharmaceuticals, Neuroderm, Novartis, Orion Pharma, Teva, UCB and Zambon (consultancy and lecture fees in relation to clinical drug development programmes for Parkinson disease) and publishing royalties from Thieme, Wiley-Blackwell, Oxford University Press and Cambridge University Press. K.S. reports personal fees from Boehringer-Ingelheim, UCB, Lundbeck, AbbVie, Roche, Teva and AOP Orphan Pharmaceuticals AG. C.M.T. has received compensation for serving on Data Monitoring Committees from Biotie Therapeutics, Voyager Therapeutics and Intec Pharma and personal fees for consulting services from Ultragenyx Pharmaceuticals, Neurocrine Biosciences, Cynapsus, Therapeutics, Sage Bionetworks and Adamas. G.M.H. has received compensation for serving on data monitoring committees from Biotie Therapeutics, Voyager Therapeutics and Intec Pharma, and personal fees from the American Academy of Neurology, Bionomics and Lundbeck. P.B. has received commercial support as a consultant from Renovo Neural, Roche, Teva, Lundbeck, AbbVie, Neuroderm, Versant Ventures/Apollo and IOS Press Partners. J.V. reports personal fees from Boston Scientific, Medtronic, Bial, Allergan, Zambon (consultancy and lecture fees in relation to clinical therapeutic development programmes for Parkinson disease) and grants from Boston Scientific and Medtronic. A.-E.S. reports grants from, Parkinson's UK, GE Healthcare, International Parkinson and Movement Disorder Society, shares from AstraZeneca, and personal fees from Grunenthal, Medtronic and Oxford University Press. A.E.L. reports personal fees from AbbVie, Acorda, Avanir Pharmaceuticals, Bristol-Myers Squibb, Cipla, Intekrin, Sun Pharma, Medichem, Medtronic, Teva, UCB and Merck, and publishing royalties from Saunders, Wiley-Blackwell, Johns Hopkins Press and Cambridge University Press.
Supplementary table 1
Imaging biomarkers for used to study Parkinson disease (PDF 107 kb)
Supplementary table 2
Overview of potential biochemical biomarkers in Parkinson disease (PDF 131 kb)
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Poewe, W., Seppi, K., Tanner, C. et al. Parkinson disease. Nat Rev Dis Primers 3, 17013 (2017). https://doi.org/10.1038/nrdp.2017.13
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