Parkinson’s disease

Epidemiology of PD

§ The most common movement disorder

affecting 1-2 % of the general population over
the age of 65 years.

§ The second most common neurodegenerative

disorder after Alzheimer s disease (AD).
 Prevalence / 100 000
Prevalence of PD

Age
Primary symptoms

• Rigidity - increased tone or stiffness in the muscles

• Tremor - 25% of patients experience very slight tremor or

none at all

• Bradykinesia - slowness of movement

• Akinesia - impaired movement initiation and poverty of

movement
Idiopathic PD inclusion Criteria
Positive criteria PD
• Resting tremor
• Progressive disorder
• Persistent asymmetry
• Excellent response to l-dopa
Idiopathic PD exclusion criteria

• History of repeated • Early severe dementia

strokes with parkinsonian • Presence of cerebral tumor
features
• Negative response to doses of
• History of head injury levodopa

• History of encephalitis
Risk factors implicated in PD

Immune
agents

Genetic
Stress

PD
factors

Heavy
Pesticides
Metals
 Etiology of Parkinson s disease

• Environmental events: chemical toxins (pesticides), metals

(Manganese, iron)

• viral/bacterial agents Poliovirus, arbovirus, herpes simplex

virus and encephalitis

• Slowly developing early viral/bacterial infection ?

• Multi-hit hypothesis
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
induced loss of TH+ SNc neurons
 MPTP

• MPTP is generally by repeated i.p. injections

• Injections closely spaced (over a single day) leads to a

30-40% loss of midbrain DAergic neurons

• If the administration is spread out over multiple days

(once or twice daily injections over 5-10 day) loss can go
to 50-70%
 MPTP

• Effective in monkeys and mice

• No Lewy bodies

• But shows some degree of bradykinesia and motor

coordination deficits

• No tremors
 6-OHDA

• Medial forebrain bundle (MFB) or the substantia nigra (SN) injections cause
DA nigral neurons to die after a few hours, and striatal DA
depletion is complete within 2-3 days.

• Intrastriatal 6-OHDA injections cause a biphasic course of

Neurodegeneration: rapid phase of DA cell death occurring within 3-7 days in
the mouse or 1 week in the rat followed by 4-6 weeks of mild additional loss.
 6-OHDA

• Not progressive like real PD

• No Lewy Bodies
• But shows pathological turning behavior when challenged with a DA agent
• Motor coordination deficits
• No tremors
 Vulnerability factors
Elevated Mitochondrial Bioenergetics and Axonal Arborization Size Are Key
Contributors to the Vulnerability of Dopamine Neurons

• Vulnerable SNc DA neurons differ in many ways from less vulnerable VTA
DA neurons

• SNc DA neurons have a higher basal rate of oxidative phosphorylation

• SNc DA neurons have a more complex axon and a higher density of

mitochondria

• Already at maximal energetic levels, hard to cope with further challenges