Parkinsons disease - Clinical and Genetic Flashcards
(33 cards)
What anatomical aspect of the brain is related to movement disorders?
Disorder of the basal ganglia.
However poor correlation between movement disorder and basal ganglial lesions
What are the names of the basal ganglia?
Substantia Nigra
Putamen
Caudate nucleus (body and tail)
Globus Palidus (internal and external)
Subthalamic nucleus
Red Nucleus
What basal ganglia is affected in Parkinsons’ disease?
Substantia Nigra
What are motor disorders sub-categorized into?
Akinetic-rigid Disorders
- e.g. Parkinsons Diseases
Hyperkinetic Disorders
- e.g. Huntingtons disease
Why should we be mindful of the organization of the basal ganglia?
Basal ganglia are interconnected with many other systems than just motor system (e.g Limbic)
So location of Stimulation of the ganglia in treatment of movement disorders can have side effects in other systems.
Cardinal motor symptoms of Parkinsons disease?
Tremor (Shaking)
Rigidity (Stiffness)
Akinesia (Slowness of movement)
Postural gait instability (balance issues)
What are the non motor symptoms associated with parkinsons?
Bladder/Bowel problems, psychiatric features, pain
What is distinctive of a Parkinson’s diseases dementia syndrome?
Transient periods of inattentiveness
Difficulties with subjective recall
Seeing objects and people who are not there (complex visual hallucinations)
What is Braak Staging and what does it do?
Braak staging is 2 methods used to classify the degree of pathology in Parkinsons and Alzheimers disease.
The stages progress with the location of Lewy Bodies in the brain, with Stage 1 having Lewy bodies confined to the brainstem and olfactory system and stage 6 having Lewy bodies spread through the neocortex.
What does each stage in Braak staging signify in terms of pathology of the disease?
Stages 1&2 - Autonomic/olfactory disturbances
Stages 3&4 - Sleep/Motor disturbances
Stages 5&6 - Emotional/cognitive disturbances
What is the difference between Parkinsons Disease and Parkinsonism?
Parkinsonism is a broad term referring to many disorders that affect movement.
Pathology (presence of Lewy Bodies) determines Parkinsons Disease
What other pathologies can elicit Parkinsonism?
Multiple systems atrophy (MSA)
Mitochondrial diseases (e.g. POLG)
Neurodegeneration with brain iron accumulation
Wilsons disease (Accumulation of copper in brain)
Neuroferritinopathy
What imaging technique would help with Ante-mortem diagnoses of Parkinsons Disease?
FP-CIT SPECT imaging of dopamine transporter. Would show a loss of dopaminergic input to striatum from substantia nigra.
What is the protein that aggregates in Parkinsons Disease and how does it propagate?
Alpha-synuclein aggregates and propagates in a prion-like manner.
What is RT-QuIC?
Real Time Quaking induced conversion - a diagnostic technique that enables detection of aSyn prions in bodily fluids.
What is the most common gene affected in familial PD?
LRRK2
Others include SNCA and parkin
What does SNCA encode and what mutations can occur?
Encodes Alpha-synuclein protein
Mutations include duplications and triplications
What does parkin encode and what is a prominent feature of pathological parkin variant?
Encodes a protein associated with mitophagy.
Dystonia (muscle spasms) are a prominent feature
What does LRRK2 encode and what is the pathway in which it causes disease?
Encodes a kinase, dardarin, which is involved in many processes
Mutations in Dardarin affect protein synthesis, autophagy, golgi sorting, synaptic vesicle endocytosis.
leads to dopamine neuron death and subsequent Parkinsons Disease
How could autophagic impairment underlie PD?
Autophagic impairment could potentially reduce the clearance of Alpha-synuclein which underlies the aggregation seen in PD
Which allele of APOE exacerbates aSyn pathology?
APOE E4
What is the function of Apolipoprotein?
Involved in the catabolism of triglyceride lipoproteins and the cholesterol transport pathway from astrocytes to neurones.
What is the biggest risk gene for sporadic PD?
GBA - encodes glucocerebrosidase (GCase)
Heterozygous variants associated with PD
Bi-allelic variants associated with Gaucher disease (build up of these cells in liver,spleen)
How does GBA influence PD?
Loss of GCase activity and lysosomal dysfunction = impaired alpha-synuclein metabolism and subsequent increase in aggregation
