Parkinson disease and Lewy body disorders
- Lesion
In Parkinson disease, dopamine neurons of the substantia nigra die and alpha-synuclein clumps form Lewy bodies, causing tremor and slowness.
What it is
Parkinson disease is the commonest cause of parkinsonism: tremor at rest, rigidity, slowness of movement and postural instability. It follows loss of dopaminergic neurons of the substantia nigra pars compacta, which project to the striatum, and is marked by Lewy bodies made of alpha-synuclein. Synuclein pathology often starts in the gut, olfactory bulb or lower brainstem before the nigra and reaches the cortex late. Dementia with Lewy bodies is the cortical end of the same spectrum; multiple system atrophy is a synucleinopathy of oligodendrocytes.
Step by step
- Alpha-synuclein misfolds, possibly first in the gut or olfactory system.
- It aggregates into Lewy neurites and Lewy bodies in vulnerable neurons.
- Mitochondrial and lysosomal dysfunction add oxidative stress to dopamine neurons.
- Nigral neurons die; dopamine falls in the striatum.
- Motor symptoms appear when most nigrostriatal terminals are gone.
- Synuclein reaches limbic and neocortical areas, with dementia in many patients.
The synucleinopathies
| Disease | Where synuclein collects | Key features |
|---|---|---|
| Parkinson disease | Neurons of brainstem, nigra, later cortex | Rest tremor, bradykinesia, rigidity; dementia late |
| Dementia with Lewy bodies | Cortical and limbic neurons | Early dementia, hallucinations, fluctuations, REM sleep behaviour disorder |
| Multiple system atrophy | Oligodendrocytes (glial cytoplasmic inclusions) | Parkinsonism or ataxia with autonomic failure |
Clinical notes
- REM sleep behaviour disorder, constipation and loss of smell can precede the motor signs by years.
- Levodopa replaces dopamine and helps motor symptoms but does not stop neuron loss.
Test yourself
Think of the answer, then tap the question to see it.
What protein is the main component of Lewy bodies?
Alpha-synuclein.
What gross change is seen in the midbrain in Parkinson disease?
Pallor of the substantia nigra from loss of pigmented dopaminergic neurons.
Where are synuclein inclusions found in multiple system atrophy?
In oligodendrocytes, as glial cytoplasmic inclusions.
Elsewhere in DurgiPedia
- Basal ganglia and movement control
- The main neurotransmitters
- The autonomic nervous system: organization
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Parkinson Disease (StatPearls (NCBI Bookshelf), 2026).
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Representative model, for educational purposes only.