Lecture 18 - Neurodegeneration

Question 1

Aetiological structure
1)
2)
3)
4)

Answer 1

1) Risk factors
2) Disease onset
3) Active disease
4) Organ failure

Question 2

What did Parkinson initially call Parkinson’s disease?

Answer 2

Shaking palsy

Question 3

Parkinson's description of shaking palsy
1)
2)
3)
4)
5)

Answer 3

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

Question 4

Which part of Parkinson’s initial description was wrong?

Answer 4

Intellect unimpaired.

Late-stage Parkinson’s has a dementia component

Question 5

When do symptoms of Parkinson’s tend to present?

Answer 5

When 50-70% of cells in substantia nigra have been lost

Question 6

What are Lewy bodies?

Answer 6

Bodies that appear in neurons, primarily made of alpha-synuclein

Question 7

Protein most associated with Parkinson’s

Answer 7

Alpha-synuclein

Question 8

Parkinson's disease simple aetiology
1)
2)
3)
4)

Answer 8

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

Question 9

Single-aetiology model

Answer 9

A single cause (EG: poliovirus) leads to condition

Not applicable to neurodegeneration

Question 10

Why are different parts of the brain injured in Parkinson’s, while others aren’t?

Answer 10

Different biochemistry, cell morphology, energy demands

Question 11

Another name for motor neurone disease

Answer 11

Amyotrophic lateral sclerosis

Question 12

Another name for amyotrophic lateral sclerosis

Answer 12

Motor neurone disease

Question 13

Effect of damaged upper motor neurons

Answer 13

Exaggerated reflexes

Weakness, paralysis

Question 14

Effect of damaged lower motor neurons

Answer 14

Wasting, weakness, paralysis, fasciculation, loss of reflexes

Question 15

What is fasciculation?

Answer 15

Localised, involuntary muscle twitch

Question 16

Reason that upper and lower motor neuron conditions have the same risks as motor neuron disease 
1)
2)
3)
4)
5)

Answer 16

1) Common embryology
2) Long axons
3) Same transmitters
4) Similar morphology
5) Similar gene expression

Question 17

Mutations in SOD1 gene

Answer 17

Associated in humans with familial motor neurone disease

In Chesapeke retriever, SOD1 mutation is associated with sensory spinal neuron pathology. Why is this different?

Question 18

Clinical signs of Parkinson's disease, from earliest to latest
1)
2)
3)
4)
5)

Answer 18

1) Sleep disorders, autonomic failure
2) Motor signs
3) Dementia
4) Impulsivity
5) Neuro-psychiatric

Question 19

Cause of PD autonomic failure

Answer 19

Lewy bodies in spinal cord, gut

Question 20

Cause of PD sleep disorders

Answer 20

Lewy bodies in the forebrain

Question 21

Cause of PD motor signs

Answer 21

Lewy bodies in the brainstem

Question 22

Cause of PD dementia, impulsivity, neuro-psychiatry

Answer 22

Lewy bodies in the thalamus, cortex

Question 23

Evidence for a disease-spread model of PD

Answer 23

Affected cells in nervous system are similar to dopamine-secreting cells.
This implies that they will have similar rates of degeneration.

Question 24

What is neurodegeneration

Answer 24

Progressive death of a subset of neurons

Question 25

What causes infantile neurodegeneration?

Answer 25

Severe genetic abnormalities

Question 26

What causes young-onset neurodegeneration?

Answer 26

Less-severe genetic abnormalities

Or increased expression of late-onset genes

Question 27

What can cause late-onset neurodegeneration?

Answer 27

Neurons can’t replicate
High energy demands of neurons, energy failing
Post fertile genes?

Question 28

Domains lost in executive dementia

Answer 28

Attention (frontal lobes), language (frontal lobe), problem solving (frontal cortex), impulsivity (frontal cortex)

Question 29

Domains lost in amnestic dementia

Answer 29

Memory (hippocampus, all cortex), attention (all cortex), language

Question 30

Another name for executive dementia

Answer 30

Frontal cortex dementia

Question 31

Another name for amnestic dementia

Answer 31

Posterior cortex dementia

Question 32

Dementia associated with PD

Answer 32

Executive dementia

Question 33

Dementia associated with Alzheimer’s

Answer 33

Amnestic dementia

Question 34

Two broad types of dementia

Answer 34

Fixed and progressive

Question 35

Problem with IDing PD and Alzheimer’s using type of dementia

Answer 35

Some PD patients have amnestic dementia

Have elevated A-beta protein