Alzheimer's and Parkinson's Diseases Flashcards
PSEN1 is the catalytic subunit of gamma-secretase. A mutation in PSEN1 causes increased production of what?
Aβ42 production is increased if PSEN1 is mutated.
Which regions of the brain are Aβ peptide deposits usually found?
Aβ peptide deposits are usually observed in the hippocampus and neocortex.
Instead of being sent to an axon, neurofibrillary tangles are sorted to…
a somatodendritic location
What does penetrance refer to?
Penetrance refers to the proportion of people with a particular genetic variant (or gene mutation) who exhibit signs and symptoms of a genetic disorder.
What does the cholinergic hypothesis state?
The cholinergic hypothesis states that deterioration in cholinergic neuron function causes the cognitive and behavioural impairments of Alzheimer’s disease.
Which type of therapies were shown to improve symptoms in Alzheimer’s patients?
Cholinesterase inhibitor therapies were shown to induce significant
symptomatic improvement in patients with Alzheimer’s disease .
How can Alzheimer’s Disease be definitively diagnosed?
Alzheimer’s Disease can be definitely diagnosed through histopathologic confirmation of the presence of Aβ plaques and neurofibrillary tangles.
When do non-motor symptoms of Parkinson’s start?
Non-motor symptoms of Parkinson’s start prior to the onset of motor symptoms, in the prodromal phase of disease.
What are the non-motor symptoms of Parkinson’s?
Non-motor symptoms of Parkinson’s include:
- disorders of sleep-wake cycle
- cognitive impairment
- disorders of mood and affect
- autonomic dysfunction, pain and hyposmia
What are the motor symptoms of Parkinson’s?
The motor symptoms of Parkinson’s include:
- resting tremor
- rigidity and stiffness
- slowness of voluntary movement (Bradykinesia)
- postural instability
What is the prodromal period in Parkinson’s?
The prodromal period is a potential temporal window for identification of biomarkers and disease modifying therapy.
What are the hallmarks of Parkinson’s disease?
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
What is the Substantia Nigra a part of?
The Substantia Nigra is part of the Basal Ganglia.
The pars compacta is a subregion of the Substantia Nigra which is responsible for what?
The pars compacta is responsible for motor control, spatial learning, temporal processing and the sleep wake cycle.
Substantia nigra neurons communicate with movement centres using dopamine therefore dopamine is crucial for…
Dopamine is crucial for the control of voluntary movements
The death of neurons in the Substantia Nigra causes which type of symptoms to arise?
The motor symptoms of Parkinson’s arise from the death of neurons in the SN.
What are Lewy bodies?
Lewy bodies are protein aggregates inside neurons which are have abnormal levels of insolubility.
What are Lewy bodies composed of?
Lewy bodies are mostly composed of α-synuclein but also include other proteins, lipids, mitochondria and vesicles.
What is α-synuclein?
α-synuclein is a presynaptic neuronal protein involved in vesicle release for synaptic transmission.
Misfolded α-synuclein sticks to other protein fragments forming clumps. What do these clumps activate?
Clumps, made from misfolded α-synuclein and other protein fragments, activate signal cascades which eventually lead to cell death.
Parkinson’s is a multifactorial disease. What are some of the molecular pathways involved?
Molecular pathways underlying Parkinson’s include:
- mitochondrial dysfunction
- lack of growth factors
- inflammation
- oxidative stress
- excitotoxicity
- protein transfer
What is the most common treatment for Parkinson’s disease?
The most common treatments for Parkinson’s are based on replacing dopamine lost because of neuron death in the Substantia Nigra.
What is the most common surgical treatment for Parkinson’s?
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.
