Parkinson's (finished) Flashcards
What are the 2 groups of brain diseases?
- Neurodegenerative
- Psychiatric
What are the characteristics of a neurodegenerative brain disease?
- Apoptosis/loss of neurones
- Disrupted/loss of (motor) function
- May also include changes in behaviour
- (e.g. AD, PD, prion disease)
What are the characteristics of a psychiatric brain disease?
- No obvious loss of neurones though may show some structural changes
- Developmental defects
- Change in behaviour
- (e.g. ADHD, ASD, SZ)
What are the 4 groups of movement disorders in the brain?
- Upper motor neuron disorders (cranium or SC)
- Lower motor neuron disorders (outside brain, muscle innervating neurons)
- Involuntary movement disorders (= dysfunction of basal ganglia)
- Cerebellar disorders
Name some upper MN disorders:
- Stroke
- Multiple Sclerosis
- Amytrophic lateral sclerosis (ALS)
Name some lower MN disorders:
- Peripheral neuropathy
- Myasthenia gravis
- Immune disease against nicotinic recpetors on muscles (NMJ)
Name some involuntary movement disorders:
- Parkinson’s disease
- Huntington’s disease
- Tremor
Name a cerebellar disorder:
Various tumor in any brain region will affect the health of the neurons present
(These cause motor dysfunction apparently)
Why is parkinsons considered to be a neurodegenerative disease?
incidence increases with age
Is parkinson considered mainly an early onset or late onset disease?
considered to be a late onset disease as most cases occur at older ages- but there is an early onset version of the disease which is predominantly caused by mutations within the genome
What is the prevalence of Parkinson’s disease?
Early onset:
40 - 60 yrs = 0.1%
>60 yrs = 0.5%
Late onset:
>85 yrs = 4%
How many patients have Parkinson’s in the UK?
Approx 125,000 ppl
Who is affected by Parkinson’s disease?
Affects all races & both sexes –> m/f at 3/2
As of 2019 - how many cases of Parkinson’s & how many deaths have there been?
8.5 million cases
330,000 deaths
How prevalent is Parkinson’s as a disabing disease?
2nd most common physically disabling disease of elderly after osteoarthiritis
(Most common neurological disabling disease)
What area is affected by Parkinson’s disease?
Neurodegeneration of extrapyramidal system
(mainly basal ganglia)
Name some symptoms of Parkinsons disease
= unable to perform normal motor function or initiate movement:
- Poor slow movement (Bradykinesia)
- Postural abnormalities
- Rigid posture
- Mask-like expression = unable to move face so do not have facial expressions
- Lack or rigidity of movement (Akinesia)
- Tremor at rest- reduces when undertaking voluntary movement
Name some later stage symptoms
Later stages also include = progression of the disease :
- Depression
- Dementia
- Endocrine dysfunction-tuberoinfundibular pathway responsible for prolactin release
What is the main neurochemical effect that causes the symptoms of parkinsons?
= Loss of striatal dopamine (single NT) within the basal ganglia
Describe the function of the basal ganglia
= programming movement
1. Stimulus to move
2. Assemble motor plan- select motor programme from memory stores + assemble appropriate sequences of motor programmes
3. Execute motor plan
Name the 4 dopamine pathways
- Nigrostriatal pathway
- Mesocortical
- mesolimbic pathways
- Tuberoinfundibular pathway
In what pathway, does parkinsons disease affect?
Nigrostriatal pathway- substantia nigra + dorsal striatum
What is the primary pathology of parkinsons disease?
Substantia nigra degeneration defined by loss of neuromelanin
What is neuromelanin?
Neuromelanin is a dark pigment found in large quantities in catecholaminergic cells of the substantia nigra pars compacta and locus coeruleus, giving a dark colour to the structures
Outline the list of changes occuring through parkinsons
- Dopamine in striatum ↓ (loss of 60-70% of dopaminergic neurons = motor symptoms)- nigrostriatal pathway = 1st characteristic of the disease
- Also loss of dopamine in mesolimbic areas (mood changes- depression, anxiety)
- Hypothalamic amines ↓= hypothalamus affected
- Cortical noradrenaline and ACh ↓ (cognitive loss)- cortical areas also affected as they are targets for dopaminergic neurons = further downstream effect within the pathogenesis
- Neuropeptides [spinal neurons, interneurons] in striatum ↓ (Substance P, Enkephalins) = neuronal dysfunction in neuroendocrine pathway
Name 2 imaging methods for diagnosing Parkinsons
PET
SPECT
What does PET stand for?
Positron Emission Tomography (PET)
How does a PET scan work in the diagnosis of Parkinsons?
Visualise and quantify dopaminergic neurones using radio-ligand (CIT) which bind to presynaptic dopamine transporter proteins (DAT)
Describe the difference in these PET scans
- Very strong signal in control
- Parkinsons brain = very strong reduction in the signal = little presynaptic DAT = indicates degeneration of neurons
What does SPECT stand for?
Single Photon Emission Computed Tomography
What is this SPECT scan showing?
Signal disappears over the period of disease progression = indicating loss of DAT = loss of presynaptic dopaminergic neurons
What is the main function of alpha-synuclein
modulates synaptic function
Describe the structure of a-synuclein and what is each structure responsible for?
Fairly small protein with 3 modular regions:
1. the N-terminal (green), responsible for interactions with membranes
2. the hydrophobic region (blue), relevant for aggregation of proteins which happens during neurodegeneration
3. the acidic C-terminal (red) involved in Ca2+ binding- responds to calcium and binds to it which affects its structure.