Parkinson’s Disease Paul Tuite, MD University of Minnesota Director of Movement Disorders
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Parkinson’s Disease Paul Tuite, MD University of Minnesota Director of Movement Disorders
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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 - PowerPoint PPT Presentation
Transcript of Parkinson’s Disease Paul Tuite, MD University of Minnesota Director of Movement Disorders
Parkinson’s Disease
Paul Tuite, MDUniversity of Minnesota
Director of Movement Disorders
Parkinson’s disease (PD)
Early Clinical FeaturesTremorSlownessStiffnessStooped postureAltered gaitSmall handwritingSoftened voiceOthers
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
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
Black line is age related loss
A. Toxin causes rapid loss of neurons at exposure
B. Genetic cause with variable rates of loss of neurons depending on the gene
C. Genetic and toxic model A H V Schapira; BMJ 1999;318:311-314
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
The Scientist 1997
PD & Environmental Factors
Increased Risk– Pesticides
• Paraquat• Organochlorines• Carbamates
– Welding– Miners
Decreased Risk– Coffee consumption
• ?Caffeine
– Smoking• Nicotine
– MAO B inhibition
– CYP2D6
Genetics Environment
Mitochondria Complex I Defects
Protein Accumulation
OxidativeStress
ExcitotoxicityAbnormal
ProteinDegradation
Cell Death
Betarbet et al. Brain Path 2002;12:499-510.
Mitochondria
Complex I Mitochondrial Inhibitors
Betarbet et al. Brain Path 2002;12:499-510.
ROTENONE
Betarbet et al. Brain Path 2002;12:499-510.
GAO 2003 inflamm in PD TIPS
Neurorestoration
Neuroprotection
Rate of development of disease
A H V Schapira; BMJ 1999;318:311-314
THERAPIES UNDER DEVELOPMENT
