Lecture 18 - Neurodegeneration Flashcards Preview

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Flashcards in Lecture 18 - Neurodegeneration Deck (35):
1

Aetiological structure
1)
2)
3)
4)

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

2

What did Parkinson initially call Parkinson's disease?

Shaking palsy

3

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

4

Which part of Parkinson's initial description was wrong?

Intellect unimpaired.
Late-stage Parkinson's has a dementia component

5

When do symptoms of Parkinson's tend to present?

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

6

What are Lewy bodies?

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

7

Protein most associated with Parkinson's

Alpha-synuclein

8

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

9

Single-aetiology model

A single cause (EG: poliovirus) leads to condition
Not applicable to neurodegeneration

10

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

Different biochemistry, cell morphology, energy demands

11

Another name for motor neurone disease

Amyotrophic lateral sclerosis

12

Another name for amyotrophic lateral sclerosis

Motor neurone disease

13

Effect of damaged upper motor neurons

Exaggerated reflexes
Weakness, paralysis

14

Effect of damaged lower motor neurons

Wasting, weakness, paralysis, fasciculation, loss of reflexes

15

What is fasciculation?

Localised, involuntary muscle twitch

16

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

17

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?

18

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

19

Cause of PD autonomic failure

Lewy bodies in spinal cord, gut

20

Cause of PD sleep disorders

Lewy bodies in the forebrain

21

Cause of PD motor signs

Lewy bodies in the brainstem

22

Cause of PD dementia, impulsivity, neuro-psychiatry

Lewy bodies in the thalamus, cortex

23

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.

24

What is neurodegeneration

Progressive death of a subset of neurons

25

What causes infantile neurodegeneration?

Severe genetic abnormalities

26

What causes young-onset neurodegeneration?

Less-severe genetic abnormalities
Or increased expression of late-onset genes

27

What can cause late-onset neurodegeneration?

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

28

Domains lost in executive dementia

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

29

Domains lost in amnestic dementia

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

30

Another name for executive dementia

Frontal cortex dementia

31

Another name for amnestic dementia

Posterior cortex dementia

32

Dementia associated with PD

Executive dementia

33

Dementia associated with Alzheimer's

Amnestic dementia

34

Two broad types of dementia

Fixed and progressive

35

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

Some PD patients have amnestic dementia
Have elevated A-beta protein