Lewy bodies are abnormal aggregations of protein that develop inside nerve cells, contributing to Parkinson's disease (PD), the Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies), and some other disorders. They are also seen in cases of multiple system atrophy, particularly the parkinsonian variant (MSA-P).
They are identified under the microscope when histology is performed on the brain. Lewy bodies appear as spherical masses that displace other cell components. Lewy bodies may be found in the brainstem (within the substantia nigra) or within the cortex. A classical Lewy body is an eosinophilic cytoplasmic inclusion consisting of a dense core surrounded by a halo of 10-nm-wide radiating fibrils, the primary structural component of which is alpha-synuclein. Cortical Lewy bodies are also composed of alpha-synuclein fibrils, but are less defined and lack halos. In histopathology, cortical Lewy bodies are a distinguishing feature for dementia with Lewy bodies (DLB), but may occasionally be seen in ballooned neurons characteristic of Pick's disease and corticobasal degeneration, as well as in patients with other tauopathies.
In 1910, Fritz Heinrich Lewy was studying in Berlin for his doctorate. He was the first doctor to notice some unusual proteins in the brain make some people act and think differently, but as of that time, scientists had not been able to determine the purpose of these proteins. His discovery became known as Lewy bodies, as published in the Handbook of Neurology in 1912, comparing them to earlier findings by Gonzalo Rodríguez Lafora. In 1913, Lafora described another case, and acknowledged Lewy as the discoverer, naming them cuerpos intracelulares de Lewy (Lewy bodies). Konstantin Nikolaevich Trétiakoff found them in 1919 in the substantia nigra of PD brains, called them corps de Lewy and is credited with the eponym. Eliasz Engelhardt argued in 2017 that Lafora should be credited with the eponym, because he named them six years before Trétiakoff. In 1923, Lewy published his findings in a book, The Study on Muscle Tone and Movement. Including Systematic Investigations on the Clinic, Physiology, Pathology, and Pathogenesis of Paralysis agitans.
According to the Journal of the History of the Neurosciences, Dr. Lewy became interested in studying more about the brain (neurology), because of the discovery that Alois Alzheimer made in 1906. The article mentions that the third reported case of Alzheimer's disease had histological structures that happened to be similar to Lewy body histology slides, but the contribution was not given to Lewy's finding.
A Lewy body is composed of the protein alpha-synuclein associated with other proteins, such as ubiquitin, neurofilament protein, and alpha B crystallin. Tau proteins may also be present, and Lewy bodies may occasionally be surrounded by neurofibrillary tangles. Lewy bodies and neurofibrillary tangles can occasionally exist in the same neuron, particularly in the amygdala.
Alpha-synuclein modulates DNA repair processes, including repair of DNA double-strand breaks (DSBs) by the process of non-homologous end joining. The repair function of alpha-synuclein appears to be greatly reduced in Lewy body bearing neurons, and this reduction may trigger cell death.
Lewy neurites are abnormal neurites in diseased neurons, containing granular material and abnormal α-synuclein filaments similar to those found in Lewy bodies. Like Lewy bodies, Lewy neurites are a feature of α-synucleinopathies such as dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. They are also found in the CA2-3 region of the hippocampus in Alzheimer's disease.
Society and culture
In the premiere episode of Boss, Dr. Ella Harris tells Chicago Mayor Tom Kane he has dementia with Lewy bodies, and his progressing symptoms are shown in each episode. In the novel The Almost Sisters by Joshilyn Jackson, one of the main characters has the disease. Academy Award winning actor Robin Williams had been diagnosed with this disease in 2014, which may have been a factor in his subsequent suicide that year.
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