Primer

Parkinson disease

  • Nature Reviews Disease Primers 3, Article number: 17013 (2017)
  • doi:10.1038/nrdp.2017.13
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Abstract

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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Acknowledgements

The authors are grateful to U. Zijerveld for providing administrative support.

Author information

Affiliations

  1. Department of Neurology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.

    • Werner Poewe
    •  & Klaus Seppi
  2. Parkinson's Disease Research Education and Clinical Center, San Francisco Veteran's Affairs Medical Center, San Francisco, California, USA.

    • Caroline M. Tanner
  3. Department of Neurology, University of California — San Francisco, San Francisco, California, USA.

    • Caroline M. Tanner
  4. Brain and Mind Centre, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.

    • Glenda M. Halliday
  5. Faculty of Medicine, University of New South Wales & Neuroscience Research Australia, Sydney, New South Wales, Australia.

    • Glenda M. Halliday
  6. Van Andel Research Institute, Center for Neurodegenerative Science, Grand Rapids, Michigan, USA.

    • Patrik Brundin
  7. Department of Neurology, University Hospital of Würzburg, Würzburg, Germany.

    • Jens Volkmann
  8. Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.

    • Anette-Eleonore Schrag
  9. Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

    • Anthony E. Lang

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Contributions

Introduction (W.P.); Epidemiology (C.M.T.); Mechanisms/pathophysiology (G.M.H., P.B. and J.V.); Diagnosis, screening and prevention (K.S. and A.-E.S.); Management (W.P., A.E.L. and J.V.); Quality of life (A.E.S.); Outlook (All); Overview of Primer (W.P.).

Competing interests

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.

Corresponding author

Correspondence to Werner Poewe.

Supplementary information

PDF files

  1. 1.

    Supplementary table 1

    Imaging biomarkers for used to study Parkinson disease

  2. 2.

    Supplementary table 2

    Overview of potential biochemical biomarkers in Parkinson disease