Alzheimer's and Parkinson's Diseases

Question 1

PSEN1 is the catalytic subunit of gamma-secretase. A mutation in PSEN1 causes increased production of what?

Answer 1

Aβ42 production is increased if PSEN1 is mutated.

Question 2

Which regions of the brain are Aβ peptide deposits usually found?

Answer 2

Aβ peptide deposits are usually observed in the hippocampus and neocortex.

Question 3

Instead of being sent to an axon, neurofibrillary tangles are sorted to…

Answer 3

a somatodendritic location

Question 4

What does penetrance refer to?

Answer 4

Penetrance refers to the proportion of people with a particular genetic variant (or gene mutation) who exhibit signs and symptoms of a genetic disorder.

Question 5

What does the cholinergic hypothesis state?

Answer 5

The cholinergic hypothesis states that deterioration in cholinergic neuron function causes the cognitive and behavioural impairments of Alzheimer’s disease.

Question 6

Which type of therapies were shown to improve symptoms in Alzheimer’s patients?

Answer 6

Cholinesterase inhibitor therapies were shown to induce significant
symptomatic improvement in patients with Alzheimer’s disease .

Question 7

How can Alzheimer’s Disease be definitively diagnosed?

Answer 7

Alzheimer’s Disease can be definitely diagnosed through histopathologic confirmation of the presence of Aβ plaques and neurofibrillary tangles.

Question 8

When do non-motor symptoms of Parkinson’s start?

Answer 8

Non-motor symptoms of Parkinson’s start prior to the onset of motor symptoms, in the prodromal phase of disease.

Question 9

What are the non-motor symptoms of Parkinson’s?

Answer 9

Non-motor symptoms of Parkinson’s include:
- disorders of sleep-wake cycle
- cognitive impairment
- disorders of mood and affect
- autonomic dysfunction, pain and hyposmia

Question 10

What are the motor symptoms of Parkinson’s?

Answer 10

The motor symptoms of Parkinson’s include:
- resting tremor
- rigidity and stiffness
- slowness of voluntary movement (Bradykinesia)
- postural instability

Question 11

What is the prodromal period in Parkinson’s?

Answer 11

The prodromal period is a potential temporal window for identification of biomarkers and disease modifying therapy.

Question 12

What are the hallmarks of Parkinson’s disease?

Answer 12

The hallmarks of Parkinson’s disease are:
1) loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc)
2) depleted dopamine levels
3) intraneuronal inclusions known as Lewy Bodies in surviving SNpc neurons

Question 13

What is the Substantia Nigra a part of?

Answer 13

The Substantia Nigra is part of the Basal Ganglia.

Question 14

The pars compacta is a subregion of the Substantia Nigra which is responsible for what?

Answer 14

The pars compacta is responsible for motor control, spatial learning, temporal processing and the sleep wake cycle.

Question 15

Substantia nigra neurons communicate with movement centres using dopamine therefore dopamine is crucial for…

Answer 15

Dopamine is crucial for the control of voluntary movements

Question 16

The death of neurons in the Substantia Nigra causes which type of symptoms to arise?

Answer 16

The motor symptoms of Parkinson’s arise from the death of neurons in the SN.

Question 17

What are Lewy bodies?

Answer 17

Lewy bodies are protein aggregates inside neurons which are have abnormal levels of insolubility.

Question 18

What are Lewy bodies composed of?

Answer 18

Lewy bodies are mostly composed of α-synuclein but also include other proteins, lipids, mitochondria and vesicles.

Question 19

What is α-synuclein?

Answer 19

α-synuclein is a presynaptic neuronal protein involved in vesicle release for synaptic transmission.

Question 20

Misfolded α-synuclein sticks to other protein fragments forming clumps. What do these clumps activate?

Answer 20

Clumps, made from misfolded α-synuclein and other protein fragments, activate signal cascades which eventually lead to cell death.

Question 21

Parkinson’s is a multifactorial disease. What are some of the molecular pathways involved?

Answer 21

Molecular pathways underlying Parkinson’s include:
- mitochondrial dysfunction
- lack of growth factors
- inflammation
- oxidative stress
- excitotoxicity
- protein transfer

Question 22

What is the most common treatment for Parkinson’s disease?

Answer 22

The most common treatments for Parkinson’s are based on replacing dopamine lost because of neuron death in the Substantia Nigra.

Question 23

What is the most common surgical treatment for Parkinson’s?

Answer 23

In early to mild stages, a surgical treatment for Parkinson’s may be used which involves implantation of a neurostimulator in basal ganglia targeted areas involved in motor control.