Lecture 18 - Neurodegeneration Flashcards
Aetiological structure 1) 2) 3) 4)
1) Risk factors
2) Disease onset
3) Active disease
4) Organ failure
What did Parkinson initially call Parkinson’s disease?
Shaking palsy
Parkinson's description of shaking palsy 1) 2) 3) 4) 5)
1) Involuntary tremulous motion
2) Lessened muscular power
3) Tremors in parts not in motion, even when supported
4) Tendency to bend trunk forwards, pass from a walking to a running pace
5) Senses, intellect unimpaired
Which part of Parkinson’s initial description was wrong?
Intellect unimpaired.
Late-stage Parkinson’s has a dementia component
When do symptoms of Parkinson’s tend to present?
When 50-70% of cells in substantia nigra have been lost
What are Lewy bodies?
Bodies that appear in neurons, primarily made of alpha-synuclein
Protein most associated with Parkinson’s
Alpha-synuclein
Parkinson's disease simple aetiology 1) 2) 3) 4)
1) Risk factors - ?
2) Disease onset - disruption in alpha-synuclein causing Lewy bodies
3) Active disease - Loss of midbrain neurons, causes impaired dopamine transmission
4) Motor symptoms
Single-aetiology model
A single cause (EG: poliovirus) leads to condition
Not applicable to neurodegeneration
Why are different parts of the brain injured in Parkinson’s, while others aren’t?
Different biochemistry, cell morphology, energy demands
Another name for motor neurone disease
Amyotrophic lateral sclerosis
Another name for amyotrophic lateral sclerosis
Motor neurone disease
Effect of damaged upper motor neurons
Exaggerated reflexes
Weakness, paralysis
Effect of damaged lower motor neurons
Wasting, weakness, paralysis, fasciculation, loss of reflexes
What is fasciculation?
Localised, involuntary muscle twitch
Reason that upper and lower motor neuron conditions have the same risks as motor neuron disease 1) 2) 3) 4) 5)
1) Common embryology
2) Long axons
3) Same transmitters
4) Similar morphology
5) Similar gene expression
Mutations in SOD1 gene
Associated in humans with familial motor neurone disease
In Chesapeke retriever, SOD1 mutation is associated with sensory spinal neuron pathology. Why is this different?
Clinical signs of Parkinson's disease, from earliest to latest 1) 2) 3) 4) 5)
1) Sleep disorders, autonomic failure
2) Motor signs
3) Dementia
4) Impulsivity
5) Neuro-psychiatric
Cause of PD autonomic failure
Lewy bodies in spinal cord, gut
Cause of PD sleep disorders
Lewy bodies in the forebrain
Cause of PD motor signs
Lewy bodies in the brainstem
Cause of PD dementia, impulsivity, neuro-psychiatry
Lewy bodies in the thalamus, cortex
Evidence for a disease-spread model of PD
Affected cells in nervous system are similar to dopamine-secreting cells.
This implies that they will have similar rates of degeneration.
What is neurodegeneration
Progressive death of a subset of neurons
What causes infantile neurodegeneration?
Severe genetic abnormalities
What causes young-onset neurodegeneration?
Less-severe genetic abnormalities
Or increased expression of late-onset genes
What can cause late-onset neurodegeneration?
Neurons can’t replicate
High energy demands of neurons, energy failing
Post fertile genes?
Domains lost in executive dementia
Attention (frontal lobes), language (frontal lobe), problem solving (frontal cortex), impulsivity (frontal cortex)
Domains lost in amnestic dementia
Memory (hippocampus, all cortex), attention (all cortex), language
Another name for executive dementia
Frontal cortex dementia
Another name for amnestic dementia
Posterior cortex dementia
Dementia associated with PD
Executive dementia
Dementia associated with Alzheimer’s
Amnestic dementia
Two broad types of dementia
Fixed and progressive
Problem with IDing PD and Alzheimer’s using type of dementia
Some PD patients have amnestic dementia
Have elevated A-beta protein
