帕金森研究进展与机制parkinsonsdisease2010课件.ppt

Parkinson’s Disease Background Best described as “shaking palsy” by James Parkinson in 1817 “Involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forwards, and to pass from a walking to a running pace: the senses and intellects being uninjured.” Neurodegenerative diseasesPrevalence in US Fast Facts about PD Annual incidence: 60,000 new cases/yr Increase with age (3% population 65 years old) Slightly more common in men Mean age at onset: 60 years old 85% of patients are over 65 years old Risk of Parkinson’s Disease Increased risk Age High Body Mass Index Male gender Family history Depression Environment factors rural living well-water drinking welding head injury Decreased risk Caffeine intake Smoking cigarettes Anti-oxidants in diet Motor Symptoms Tremor at rest Bradykinesia Rigidity Postural instability Decreased arm swing when walking Micrographia Hypophonia Masked face Slow, shuffling gait Stooped posture “…the hand failing to answer with exactness to the dictates of the will.” Manifestations of PD Additional Features Cognitive, mood, and behavioral dysfunction Olfactory disturbance Sleep disturbance Constipation Seborrheic dermatitis Pain Autonomic disturbances Diagnosing PD United Kingdom Brain Bank Criteria Stage I Hoehn and Yahr (HY)- unilateral Stage II HY – bilateral Stage III HY – bilateral with loss of balance/falls Stage IV HY – all above and significant disability Stage V HY- bedbound Parkinson’s Disease Pathology CNS Motor Organization Pyramidal system Weakness Extrapyramidal system Modulator of pyramidal system Symptoms involuntary movement slow, interrupted movement ? posture/tone Parkinson’s Disease Dopamine deficiency in PDPET scan Braak Staging of PD Alpha-Synuclein Pathology in the Substantia Nigra and Neocortex Alpha Synuclein Toxic Alpha-synuclein Chaperones prevent toxic alpha-synuclein from forming Develop antibodies that keep alpha-synuclein