Lewy bodies (LBs) are hallmark intracellular inclusions characteristic of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). These proteinaceous aggregates primarily consist of alpha-synuclein (α-syn) along with numerous other proteins, lipids, and cellular components. Understanding Lewy body formation is crucial for elucidating PD pathogenesis and developing disease-modifying therapies[@spillantini1997].
Lewy Body Biology
Morphology and Classification
flowchart TD
A["Lewy Body Formation"] --> B["Soluble alpha-Syn Monomers"]
B --> C["alpha-Syn Misfolding"]
C --> D["Oligomeric Intermediates"]
D --> E["Protofibrils"]
E --> F["Fibrillar Aggregates"]
F --> G["Lewy Bodies"]
G --> H["Classical LBs"]
G --> I["Cortical LBs"]
G --> J["Incidental LBs"]
Types of Lewy Bodies
| Type | Location | Characteristics | |------|----------|-----------------| | Classical (Brainstem) | Substantia nigra, locus coeruleus | Dense core, halos, ubiquitin-positive | | Cortical | Cerebral cortex | Diffuse, less organized | | Transitional | Limbic system | Intermediate features |
Ultrastructure
Core: Densely packed, 8-10 nm diameter fibrils
Halo: Radiating fibrils, 80-200 nm wide
Membranous organelles: Mitochondria, lysosomes, ER fragments
Lipid membranes: Disrupted cellular membranes
Molecular Composition
Primary Components
Alpha-Synuclein
...
Lewy Body Formation Pathway
Overview
Lewy bodies (LBs) are hallmark intracellular inclusions characteristic of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). These proteinaceous aggregates primarily consist of alpha-synuclein (α-syn) along with numerous other proteins, lipids, and cellular components. Understanding Lewy body formation is crucial for elucidating PD pathogenesis and developing disease-modifying therapies[@spillantini1997].
Lewy Body Biology
Morphology and Classification
Mermaid diagram (expand to render)
Types of Lewy Bodies
| Type | Location | Characteristics | |------|----------|-----------------| | Classical (Brainstem) | Substantia nigra, locus coeruleus | Dense core, halos, ubiquitin-positive | | Cortical | Cerebral cortex | Diffuse, less organized | | Transitional | Limbic system | Intermediate features |
Ultrastructure
Core: Densely packed, 8-10 nm diameter fibrils
Halo: Radiating fibrils, 80-200 nm wide
Membranous organelles: Mitochondria, lysosomes, ER fragments
Müller J et al. (2026 Dec) [A cell type enrichment analysis tool for brain DNA methylation data (CEAM).](https://pubmed.ncbi.nlm.nih.gov/41428862/). Epigenetics*
Lozupone M et al. (2026 Apr 1) [Neuropsychiatric symptoms and apolipoprotein E genotypes in neurocognitive disorders.](https://pubmed.ncbi.nlm.nih.gov/40145985/). Neural Regen Res*
Armakola M et al. (2026 Mar 11) [In Vivo Screen of Parkinson's Disease GWAS Risk Genes Identifies ARIH2 as a Novel Regulator of α-Synuclein Toxicity in Dopaminergic Neurons.](https://pubmed.ncbi.nlm.nih.gov/41651665/). J Neurosci*
Kim JH et al. (2026 Mar 10) [Ultrasonic repression of TRPA1-dependent astrocyte reactivity confers neuroprotection in models of Lewy body dementia.](https://pubmed.ncbi.nlm.nih.gov/41808144/). Transl Neurodegener*
Vrillon A et al. (2026 Mar 10) [Association of (18)FFlortaucipir-PET and Plasma [p-Tau217](/biomarkers/p-tau-217) With [Tau](/proteins/tau) Neuropathology in Alzheimer Disease and Other Neurodegenerative Disorders.](https://pubmed.ncbi.nlm.nih.gov/41628396/). Neurology*
[UniProt](https://www.uniprot.org/) - Protein database
References
[Spillantini MG, Schmidt ML, Lee VM, et al., Alpha-synuclein in Lewy bodies. Nature. 1997;388(6645):839-840 (1997)](https://doi.org/10.1038/42166)
[Braak H, Del Tredici K, Rüb U, et al., Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003;24(2):197-211 (2003)](https://doi.org/10.1016/s0197-4580(02)
[Lashuel HA, Overk CR, Oueslati A, et al., The many faces of alpha-synuclein: from structure and toxicity to therapeutic target. Nat Rev Neurosci. 2013;14(1):38-48 (2013)](https://doi.org/10.1038/nrn3406)
[Unknown, Recasens A, Dehay B. Alpha-synuclein spreading in Parkinson's disease. Front Neuroanat. 2014;8:159 (2014)](https://doi.org/10.3389/fnana.2014.00159)
[Unknown, Wong YC, Krainc D. Alpha-synuclein toxicity in neurodegeneration. Nat Med. 2017;23(1):1-13 (2017)](https://doi.org/10.1038/nm.4269)
[Unknown, Bendor JT, Logan TP, Edwards RH. The function of alpha-synuclein. Neuron. 2013;79(6):1044-1066 (2013)](https://doi.org/10.1016/j.neuron.2013.08.033)
[Villar-Piqué A, da Silva FL, Ventura S, et al., Alpha-synuclein amyloids in Parkinson's disease. Prog Mol Biol Transl Sci. 2015;133:169-202 (2015)](https://doi.org/10.1016/bs.pmbts.2015.06.004)
[Cheng J, Liao Y, Dong H, et al., Immunotherapy targeting alpha-synuclein aggregation. Nat Rev Neurol. 2022;18(12):691-703 (2022)](https://doi.org/10.1038/s41582-022-00690-7)