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Milestones in Parkinson's disease—Clinical and pathologic features


  • Glenda Halliday PhD,

    1. Neuroscience Research Australia and the University of New South Wales, Sydney, Australia
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  • Andrew Lees MD, FRCP,

    Corresponding author
    1. University College London, Reta Lila Weston Institute of Neurological Studies, London, United Kingdom
    • University College London, Reta Lila Weston Institute of Neurological Studies, 1 Wakefield Street, London WC1N 1PJ, UK
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  • Matthew Stern MD

    1. University of Pennsylvania Health Systems, Pennsylvania Hospital, Department of Neurology, Philadelphia, Pennsylvania, USA
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  • Relevant conflicts of interest/financial disclosures: Glenda Halliday is a Senior Principal Research Fellowship of the National Health and Medical Research Council of Australia (fellowship #350827). Andrew Lees receives funding from the Weston Trust and the PSP (Europe) Association. Matthew Stern is a consultant to Teva, Medtronic, Ipsen, Schering-Plough, Adamas, and Novartis.

    Full financial disclosures and author roles may be found in the online version of this article.


The identification of the widespread deposition of fibrillized α-synuclein in Lewy bodies and Lewy neurites in the brains of patients with Parkinson's disease in 1997 has had a profound impact on how the disease is now conceptualized. The previous focus on the loss of the dopaminergic nigrostriatal system, the concept of subcortical dementia, and the idea that Parkinson's disease was dominated by motor impairment have all given way to research assessing more diverse brain regions, clinical symptoms, and phenotypes. It is now recognized that Parkinson's disease is more than just a loss of midbrain dopaminergic neurons in association with Lewy bodies. There are now several theories on how the disease develops and progresses currently being validated in a variety of studies, although many of these theories have yet to incorporate the phenotypic clinical and pathological changes associated with age. A particularly exciting new area of research involves the cell-to-cell transmission of pathogenic proteins. The recent consensus definition of Parkinson's disease dementia will allow its pathologic substrates to be determined. These advances have progressed to a stage where the preclinical stages of Parkinson's disease and its specific signs and symptoms are being predicted and tested clinically. Such strategies herald a future wave of preventive strategies for Parkinson's disease and its clinical symptoms. © 2011 Movement Disorder Society

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