Neurodegenerative Conditions

Question 1

Describe the genetic component of Huntington’s

Answer 1

Dominant inheritance. Only need one copy. Child of parent who has it= 50% of getting it

Question 2

How many repetitions of the HTT protein guarantees the development of HD?

Answer 2

Over 40

Question 3

What is a defining symptom of HD?

Answer 3

Chorea

Question 4

List some symptoms of HD

Answer 4

Bradykinesia, cognitive impairment, dementia, chorea, depression

Question 5

Describe chorea

Answer 5

Abnormal, involuntary movement of the muscles (Particularly in the hands, feet and face)

Question 6

What is the prodromal phase of HD?

Answer 6

This is where the symptoms first appear, just before diagnosis

Question 7

HD is recognisable by the degeneration and atrophy of the…..

Answer 7

Striatum

Question 8

How does impairment of proteostasis cause cell death in neurons? In HD

Answer 8

Impaired proteostasis = impairment of the cell’s waste removal system. Leads to a toxic build up of damaged proteins and other cell waste products.

Question 9

Explain the use of tetrabenazine in Huntington’s

Answer 9

Treats chorea by reducing dopamine in the brain

Question 10

Describe the 2 ways that tetrabenazine reduces dopamine in the brain

Answer 10

• binds to VMATs to prevent dopamine from entering vesicles for exocytosis
• competitive antagonist to post-synaptic dopamine receptors

Question 11

Define VMAT

Answer 11

Vesicular mono-amine transporters

Question 12

What is the acronym that describes the symptoms experienced in Parkinson’s disease?

Answer 12

TRAP 
T- tremor at rest 
R- rigidity of limbs 
A - akinesia (loss of voluntary muscle control)
P - postural problems

Question 13

Which symptoms usually occur first in Parkinson’s?

Answer 13

Sleep issues, depression, anxiety, etc

Question 14

Loss of dopaminergic neurons in which area of the brain is a hallmark for Parkinson’s?

Answer 14

Substantia nigra

Question 15

Accumulation of alpha-synuclein is a hallmark for which disease?

Answer 15

Parkinson’s

Question 16

How can staining of brain tissue from the substantia nigra identify Parkinson’s?

Answer 16

Staining healthy brain tissue would reveal more cell bodies than in Parkinson’s brain tissue, showing the death of neurons

Question 17

How is dopamine related to the movement symptoms of Parkinson’s?

Answer 17

Death of dopaminergic neurons in the brain lead to a dopamine deficiency. (Remember dopamine is an inhibitory neurotransmitter) this leads to the increased activity of excitatory neurotransmitters, causing the movement abnormalities

Question 18

Name the goal of pharmacological treatment in Parkinson’s

Answer 18

To stabilise the neurotransmitters. To increase dopamine and decrease excitatory NTs like acetylcholine

Question 19

Describe the mechanism of action of carbidopa and benserazide (first line drugs for Parkinson’s)

Answer 19

Prevent the peripheral metabolism of dopamine by blocking an enzyme

Question 20

How does rasagiline work? What condition is it used for?

Answer 20

Used in Parkinson’s
Blocks MAO-B (enzyme that breaks down dopamine) in the synaptic cleft, which prolongs dopamine’s action in the synaptic cleft

Question 21

Deep brain stimulation using high frequencies can help with which side effect of Parkinson’s?

Answer 21

Dyskinesia

Question 22

Amyloid-beta plaques are a defining feature of….

Answer 22

Alzheimer’s

Question 23

What is the consequence of the formation of beta-amyloid plaques

Answer 23

Death of nerve cells

Question 24

An MRI scan of an Alzheimer’s patient would show degradation and atrophy in which area of the brain?

Answer 24

Cortical

Question 25

Other than amyloid-beta plaques, which mechanism leads to Alzheimer’s?

Answer 25

Tau neurofibrillary tangles

Question 26

How do cholinesterase inhibitors work in Alzheimer’s?

Answer 26

Increase the concentration of acetylcholine at the synapse, working to improve memory and attention

Question 27

How do focal ultrasounds work in Alzheimer’s?

Answer 27

They penetrate and open up the BBB, reducing amyloid beta plaques which can reduce memory deficits

Question 28

Which neurodegenerative disease has the lowest post-diagnosis life expectancy?

Answer 28

ALS

Question 29

What does ALS stand for

Answer 29

Amyotrophic lateral sclerosis

Question 30

Patients with undiagnosed ALS will often present to their doctor with which symptom?

Answer 30

Weakened muscles
Could be affecting their daily lives
- falling over
- decreased fine motor abilities

Question 31

The onset of ALS is usually…

Answer 31

Focal - concentrated in one area of the body

Question 32

ALS hallmark / defining feature is the degradation of…

Answer 32

Upper and lower motor neurons. Causes less inner action of the skeletal muscle, leading to weakness (including diaphragm)

Question 33

Explain the use of riluzole

Answer 33

Used in ALS.

Inhibits excitatory neurotransmitters (like glutamic acid) and inhibits voltage gated sodium channels

Question 34

Which condition is associated with the striatum

Answer 34

Huntington’s

Question 35

Parkinson’s affects which area of the brain

Answer 35

Substantia nigra

Question 36

Which condition = atrophy of the cortical region

Answer 36

Alzheimer’s

Question 37

What causes ALS motor neuron degeneration?

Answer 37

Hypermetabolism of the neuron

Question 38

Name the 2 proteins associated with Alzheimer’s

Answer 38

Tau neurofibrillary tangles and beta amyloid plaques

Question 39

What protein is associated with Parkinson’s disease

Answer 39

Lewy bodies

Question 40

Cause of neuronal cell death in Huntington’s

Answer 40

Impaired proteostasis

Question 41

Why would benzatropine be useful in Parkinson’s

Answer 41

It is an acetylcholine antagonist. So it reduces excitation, which levels out the inhibition / excitation imbalance present in parksions due to insufficient dopamine