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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
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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
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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
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.