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Parkinson’s Disease Paul Tuite, MD University of Minnesota Director of Movement Disorders

Parkinson’s Disease Paul Tuite, MD University of Minnesota Director of Movement Disorders. Parkinson’s disease (PD). Early Clinical Features Tremor Slowness Stiffness Stooped posture Altered gait Small handwriting Softened voice Others. Epidemiology of PD. Incidence

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Parkinson’s Disease Paul Tuite, MD University of Minnesota Director of Movement Disorders

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  1. Parkinson’s DiseasePaul Tuite, MDUniversity of MinnesotaDirector of Movement Disorders

  2. Parkinson’s disease (PD) Early Clinical Features Tremor Slowness Stiffness Stooped posture Altered gait Small handwriting Softened voice Others

  3. Epidemiology of PD • Incidence • 5-24/ 105 worldwide (USA: 20.5/105) • Incidence of PD rising slowly with aging population • Prevalence • 57-371/105 worldwide (USA/Canada 300/105) • 35%-42% of cases undiagnosed at any time • Onset • mean PD 62.4 years • rare before age 30; 4-10% cases before age 40 www.wemove.org

  4. Risk Factors • Definite: Old age • Highly likely: MZ co-twin with early-onset PD • Probable: Positive family history • Possible: Herbicides, pesticides, heavy metals, proximity to industry, rural residence, well water, repeated head trauma, etc. • Possible protective effect: Smoking www.wemove.org

  5. Black line is age related loss • Toxin causes rapid loss of neurons at exposure • Genetic cause with variable rates of loss of neurons depending on the gene • Genetic and toxic model A H V Schapira; BMJ 1999;318:311-314

  6. Genetics of PD • PARK1: (dominant), 4q21: alpha-synuclein • PARK2: (mainly recessive) 6q25-q27: Parkin • PARK3: (dominant, reduced penetrance) 2p13 • PARK4: (dominant, early onset) 4p15 • PARK5: (susceptibility gene) 4p14: UCH-L1 • PARK6: (recessive) 1p35-p36 • PARK7: (recessive) 1p36 • PARK8: (dominant) 12p11 • PARK9: (Kufor-Rukeb syndrome; recessive) 1p36 • PARK10: (susceptibility gene) 1p32 • FTDP17: (susceptibility gene) 17q21: Tau

  7. The Scientist 1997

  8. Increased Risk Pesticides Paraquat Organochlorines Carbamates Welding Miners Decreased Risk Coffee consumption ?Caffeine Smoking Nicotine MAO B inhibition CYP2D6 PD & Environmental Factors

  9. Genetics Environment Mitochondria Complex I Defects Abnormal Protein Degradation Oxidative Stress Excitotoxicity Cell Death Protein Accumulation Betarbet et al. Brain Path 2002;12:499-510.

  10. Mitochondria

  11. Complex I Mitochondrial Inhibitors Betarbet et al. Brain Path 2002;12:499-510.

  12. ROTENONE

  13. Betarbet et al. Brain Path 2002;12:499-510.

  14. GAO 2003 inflamm in PD TIPS

  15. THERAPIES UNDER DEVELOPMENT Rate of development of disease Neurorestoration Neuroprotection A H V Schapira; BMJ 1999;318:311-314

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