Wk.6 L1 - Parkinson's disease Flashcards
(13 cards)
LO
- Describe the clinical symptoms and pathological hallmarks of Parkinson disease
- Explain what is known about disease aetiology and risk factors
- Explain how degeneration in basal ganglia movement circuits contributes to symptoms
Epidemiology
- Affects 1% of persons >60 years
- Fastest growing neurological disorder
- Massive burden $8.9b
- No cure or disease-modifying treatments
- Diagnosis is based on clinical observation and treatment response
Symptoms
Movement disorder
Classic triad:
- Muscle ridgidity
- Tremors
- Akinesia/ Bradykinesia
Neuropathology
- Progressive death of dopamine neurons in substantia nigra
- Deposition of abnormal forms of protein (α-
synuclein, superoxide dismutase 1, tau)
- Aggregated α-synuclein forms Lewy bodies in Parkinson brain
[heft]
Causes of PD
Approx. 90% cases are idiopathic
Approx. 10% are genetic/familial disease (inherited)
- e.g. mutations in gene for α-synuclein protein
α-synuclein and PD
In a healthy brain α-synuclein is located in synapses
In Parkinson disease brain α-synuclein becomes insoluble and deposits in cell bodies, forming Lewy bodies
Risk modifiers
Multifactorial
- Genetic
- Env.
- Lifestyle
Motor circuitry in health and Parkinson disease
- PD changes the movement disorder in brain
- Basal ganglia consists of different regions in the brain which are wired with axon pathways
- Substantia nigra pars compacta is where the cell bodies of dopamine neurons are found
- Dopamine released into the striatum modifies activity of 2 pathways: Direct and Indirect pathways
- Normally activity is well balanced between pathways, in PD doponomonergic neurons in substantia die (less dopamine released)
- Higher indirect pathway activity, leading to tremors, slowness and rigidity
Direct pathway (fascilitates movement)
- From stiatum to globus pallidus
- Globus pallidus to thalamus
- Thalamus to Motor cortex
Indirect pathway (Inhibits movement)
- From striatum to globus pallidus externus
- Globus pallidus externus to subthalamic nucleus
- Subthalamic nucleus to Globus Pallidus
- Globus pallidus to thalamus
- Thalamus to Motor cortex
Why Substantia nigra dopamine neurons die
Essentially we don’t know
Strong hypotheses include:
* Neuroinflammation
* Biometal dyshomeostasis
* Proetin aggregation
* Lysosome dysfunction
* etc.
Curing PD needs more than a treatment
- Need to find a way of preventing or slowing the death of the dopomonogenic cells (challenging with depth of the disorder)
- Disease process could be 20 years before diagnosis
- Need to identify disease very early on to stop neuron death
α-Synuclein seed amplification assay - a biomarker?
Helping identify PD early
Takes blood or CSF from patient containing seeds of α-Synuclein protein
Samples can be incubates with more α-Synuclein to develope immature lewy bodies
Rate of amplification corresponds to faster seed produced and characteristics of PD
Cant be used to diagnose yet, don’t know if its accurate enough
