Parkinson’s Disease
Parkinson’s Disease — Neurodegeneration in Motion
From the substantia nigra and α-synuclein to levodopa, deep brain stimulation, and the disease-modifying frontier — eight integrating modules.
Why a course on Parkinson’s?
Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s and the commonest neurodegenerative movement disorder. Its prevalence approaches 1% of those over 60 and rises to ~3% over 80. Globally, ~10 million people live with PD and incidence is rising faster than any other neurological disease — doubling between 1990 and 2016 (GBD 2019).
Two centuries after James Parkinson’s 1817 Essay on the Shaking Palsy, PD remains the disease most defined by its anatomy: the loss of pigmented dopaminergic neurons in the substantia nigra pars compacta. This course traces the biology — α-synuclein proteostasis, mitochondrial quality control, the GBA–LRRK2 lysosomal axis — through to the levodopa era opened by Carlsson and Cotzias, deep brain stimulation by Benabid, and the disease-modifying trials now in late-phase development. It cross-references Alzheimer’s Disease, Neuroscience, Cell Physiology, Pharmacology, and Stroke.
Course Parts
Overview & Epidemiology
James Parkinson’s 1817 essay; the most common neurodegenerative movement disorder; ~1% prevalence over age 60; the cardinal TRAP features; rising incidence; global cost of care.
Neuroanatomy & Basal Ganglia
Substantia nigra pars compacta, the nigrostriatal dopamine pathway, direct/indirect basal ganglia loops, and the model of bradykinesia. MPTP and the Langston cohort.
α-Synuclein & Lewy Bodies
SNCA gene, intrinsically disordered α-synuclein, Lewy body cryo-EM, Braak staging of PD pathology, the prion-like spread hypothesis, the gut-brain vagal axis.
Genetics
Autosomal-dominant SNCA and LRRK2; recessive PRKN, PINK1, DJ-1; the GBA risk allele; GWAS architecture; heritability estimates.
Clinical Features & Phenotypes
Motor (TRAP, freezing, festination) and non-motor (RBD, hyposmia, dysautonomia, depression, dementia) features; tremor-dominant vs PIGD subtypes; Hoehn-Yahr; atypical parkinsonism.
Diagnosis
MDS Clinical Diagnostic Criteria 2015, DAT-SPECT (DaTscan), red-flag MRI signs (hummingbird, hot-cross-bun), genetic testing, RBD as a prodromal window.
Therapy
Carlsson’s Nobel and the L-DOPA story; dopamine agonists; MAO-B and COMT inhibitors; motor fluctuations and dyskinesias; Benabid’s deep brain stimulation; LCIG, focused ultrasound.
Future Directions
Anti-α-synuclein antibodies (prasinezumab, cinpanemab), GBA-targeted ambroxol/venglustat, LRRK2 inhibitors, AAV gene therapy, the Kyoto stem-cell trial, exercise & microbiome.
What you’ll learn
- Distinguish idiopathic PD from atypical parkinsonism (PSP, MSA, CBD, DLB).
- Trace the nigrostriatal pathway and explain the direct/indirect basal-ganglia loops.
- Reason about α-synuclein aggregation, fibril polymorphs, and prion-like spread.
- Predict the impact of GBA, LRRK2, and SNCA variants on age of onset and phenotype.
- Apply the MDS 2015 clinical diagnostic criteria and interpret a DaTscan.
- Compute LEDD and design a levodopa schedule that minimises fluctuations and dyskinesia.
- Counsel a patient on STN-DBS eligibility, expected motor benefit, and risks.
- Critically evaluate the disease-modifying trial pipeline (prasinezumab, ambroxol, LRRK2-i).
Prerequisites
Working knowledge of CNS anatomy, neurotransmitter pharmacology, and basic biochemistry of proteostasis. The course cross-references Neuroscience, Cell Physiology, and Pharmacology.