Parkinson's Parkinson's Research and Pathophysiology 1 — Questions and Answers
Question 1: Which genetic mutation is the most common known cause of familial Parkinson's disease in the US and Europe?
- LRRK2 (leucine-rich repeat kinase 2) mutation (Correct answer)
- PINK1 mutation
- Parkin mutation
- SNCA duplication
Correct answer: LRRK2 (leucine-rich repeat kinase 2) mutation
LRRK2 mutations, particularly G2019S, are the most common genetic cause of familial Parkinson's disease in Western populations, accounting for about 1% of all Parkinson's cases.
Question 2: The Braak staging system for Parkinson's disease describes:
- The caudal-to-rostral spread of Lewy body pathology through the brain (Correct answer)
- The severity of tremor
- The progression of cognitive decline
- The response to dopaminergic therapy
Correct answer: The caudal-to-rostral spread of Lewy body pathology through the brain
Braak staging proposes that Parkinson's pathology (Lewy bodies) begins in the gut and lower brainstem and spreads upward through the brain in a predictable pattern across six stages.
Question 3: What is the current leading hypothesis for how alpha-synuclein pathology spreads in Parkinson's disease?
- Prion-like cell-to-cell transmission (Correct answer)
- Blood-borne spread via circulation
- Viral infection spread
- Immune-mediated attack
Correct answer: Prion-like cell-to-cell transmission
The prion-like hypothesis proposes that misfolded alpha-synuclein propagates from cell to cell like a prion, seeding aggregation in neighboring neurons.
Question 4: Mitophagy dysfunction in Parkinson's disease is linked to mutations in which two genes?
- PINK1 and Parkin (Correct answer)
- LRRK2 and SNCA
- GBA and DJ-1
- ATP13A2 and UCHL1
Correct answer: PINK1 and Parkin
PINK1 and Parkin work together in a mitophagy pathway to clear damaged mitochondria; mutations in either gene cause autosomal recessive Parkinson's disease.
Question 5: GBA gene mutations in Parkinson's disease are significant because they:
- Are the most common genetic risk factor for Parkinson's disease overall (Correct answer)
- Cause the mildest form of Parkinson's
- Are only found in Ashkenazi Jewish populations
- Have no effect on disease progression
Correct answer: Are the most common genetic risk factor for Parkinson's disease overall
GBA mutations (causing glucocerebrosidase enzyme deficiency) are the most common genetic risk factor for Parkinson's disease, found in 5–15% of patients, and are associated with faster progression.
Question 6: The gut-brain axis hypothesis of Parkinson's disease suggests that the disease may originate in:
- The enteric nervous system of the gut (Correct answer)
- The peripheral motor neurons
- The cerebellum
- The thalamus
Correct answer: The enteric nervous system of the gut
The gut-brain hypothesis, supported by Braak staging and epidemiological data, proposes that Parkinson's pathology may begin in the enteric nervous system and travel via the vagus nerve to the brain.
Parkinson's Parkinson's Research and Pathophysiology 1
Which genetic mutation is the most common known cause of familial Parkinson's disease in the US and Europe?