[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Central nervous system](https://durgical.com/en/general-pathology/areas/cns/) › Parkinson disease and Lewy body disorders

# 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.

Updated Nov 12, 2026

## Key points

- Gross: pallor of the substantia nigra and locus coeruleus from loss of pigmented neurons.
- Lewy body: round eosinophilic cytoplasmic inclusion with a dense core and pale halo; alpha-synuclein and ubiquitin positive.
- Genes: SNCA (alpha-synuclein), LRRK2 (commonest dominant), PRKN and PINK1 (recessive, mitochondrial quality control), GBA1 risk variants.
- Toxin model: MPTP, a contaminant of illicit opioids, kills nigral neurons.
- Dementia with Lewy bodies: dementia before or within a year of parkinsonism, visual hallucinations, fluctuating attention; cortical Lewy bodies.
- Multiple system atrophy: glial cytoplasmic inclusions of synuclein in oligodendrocytes; parkinsonism, ataxia and autonomic failure.

## 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](https://durgical.com/en/conditions/parkinson-disease/) | Neurons of brainstem, nigra, later cortex | Rest tremor, bradykinesia, rigidity; dementia late |
| [Dementia with Lewy bodies](https://durgical.com/en/conditions/dementia-with-lewy-bodies/) | Cortical and limbic neurons | Early dementia, hallucinations, fluctuations, REM sleep behaviour disorder |
| [Multiple system atrophy](https://durgical.com/en/conditions/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.

## Memory aid

Pale nigra, pink Lewy: the substantia nigra loses its colour while Lewy bodies glow pink in the survivors.

## 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.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/parkinson-disease-and-lewy-body-disorders/)

[More Pathology questions →](https://durgical.com/en/practice/?f=pathology)

## Elsewhere in DurgiPedia

- [Basal ganglia and movement control](https://durgical.com/en/physiology/basal-ganglia-and-movement-control/)
- [The main neurotransmitters](https://durgical.com/en/physiology/the-main-neurotransmitters/)
- [The autonomic nervous system: organization](https://durgical.com/en/physiology/the-autonomic-nervous-system-organization/)

## Connections

## Related 5

- [Neurodegeneration: the protein table](https://durgical.com/en/general-pathology/neurodegeneration-the-protein-table/)
- [Frontotemporal lobar degeneration](https://durgical.com/en/general-pathology/frontotemporal-lobar-degeneration/)
- [Alzheimer disease: plaques and tangles](https://durgical.com/en/general-pathology/alzheimer-disease-plaques-and-tangles/)
- [Metabolic and toxic brain injury](https://durgical.com/en/general-pathology/metabolic-and-toxic-brain-injury/)
- [Pigments in tissue: lipofuscin, hemosiderin, melanin, bilirubin, carbon](https://durgical.com/en/general-pathology/pigments-in-tissue-lipofuscin-hemosiderin-melanin-bilirubin-carbon/)

## Related conditions 6

- [Parkinson disease](https://durgical.com/en/conditions/parkinson-disease/)
- [Dementia with Lewy bodies](https://durgical.com/en/conditions/dementia-with-lewy-bodies/)
- [Multiple system atrophy (MSA)](https://durgical.com/en/conditions/multiple-system-atrophy/)
- [REM sleep behaviour disorder (RBD)](https://durgical.com/en/conditions/rem-sleep-behaviour-disorder/)
- [Progressive supranuclear palsy](https://durgical.com/en/conditions/progressive-supranuclear-palsy/)
- [Dementia (major neurocognitive disorder)](https://durgical.com/en/conditions/dementia/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

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](https://www.ncbi.nlm.nih.gov/books/NBK470193/) (StatPearls (NCBI Bookshelf), 2026).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/general-pathology/parkinson-disease-and-lewy-body-disorders/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/parkinson-disease-and-lewy-body-disorders/