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Lewy body

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Photomicrographs of regions of substantia nigra in this Parkinson's patient show Lewy bodies and Lewy neurites in various magnifications. Top panels show a 60-times magnification of the alpha-synuclein intraneuronal inclusions aggregated to form Lewy bodies. The bottom panels are 20x magnification images that show strand-like Lewy neurites and rounded Lewy bodies of various sizes. Neuromelanin-laden cells of the substantia nigra are visible in the background. Stains used: mouse monoclonal alpha-synuclein antibody; counterstained with Mayer's haematoxylin
Lewy bodies

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).[1]

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,[2] as well as in patients with other tauopathies.[3]

History

In 1910, Fritz Heinrich Lewy was studying in Berlin for his doctorate.[4] 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,[5] comparing them to earlier findings by Gonzalo Rodríguez Lafora.[6] In 1913, Lafora described another case, and acknowledged Lewy as the discoverer, naming them cuerpos intracelulares de Lewy (Lewy bodies).[6] 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.[6] Eliasz Engelhardt argued in 2017 that Lafora should be credited with the eponym, because he named them six years before Trétiakoff.[6] 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.[7]

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.[8]

Cell biology

Photomicrograph of the dorsal motor nucleus of the vagus nerve (DmX) in a transverse section along the upper medulla shown to be affected by the abnormally deposited alpha synuclein as part of intraneuronal Lewy bodies found (extreme right): DmX is one of the earliest sites affected by synuclein deposition in Parkinson's disease.[9]

A Lewy body is composed of the protein alpha-synuclein associated with other proteins, such as ubiquitin,[10] neurofilament protein, and alpha B crystallin. Tau proteins may also be present, and Lewy bodies may occasionally be surrounded by neurofibrillary tangles.[11][12] Lewy bodies and neurofibrillary tangles can occasionally exist in the same neuron, particularly in the amygdala.[13]

Lewy bodies are believed to represent an aggresome response in the cell.[14]

Alpha-synuclein modulates DNA repair processes, including repair of DNA double-strand breaks (DSBs) by the process of non-homologous end joining.[15] 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

Lewy neurites are abnormal neurites in diseased neurons, containing granular material and abnormal α-synuclein filaments similar to those found in Lewy bodies.[16] Like Lewy bodies, Lewy neurites are a feature of α-synucleinopathies such as dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy.[17] They are also found in the CA2-3 region of the hippocampus in Alzheimer's disease.[17]

Society and culture

Further information: Lewy body dementia § 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.

See also

References

  1. ^ Jellinger KA (September 2007). "More frequent Lewy bodies but less frequent Alzheimer-type lesions in multiple system atrophy as compared to age-matched control brains". Acta Neuropathologica. 114 (3): 299–303. doi:10.1007/s00401-007-0227-4. PMID 17476513.
  2. ^ Dickson DW, Feany MB, Yen SH, Mattiace LA, Davies P (1996). "Cytoskeletal pathology in non-Alzheimer degenerative dementia: new lesions in diffuse Lewy body disease, Pick's disease, and corticobasal degeneration". Journal of Neural Transmission. Supplementum. Journal of Neural Transmission Supplement. 47: 31–46. doi:10.1007/978-3-7091-6892-9_2. ISBN 978-3211828236. PMID 8841955.
  3. ^ Popescu A, Lippa CF, Lee VM, Trojanowski JQ (December 2004). "Lewy bodies in the amygdala: increase of alpha-synuclein aggregates in neurodegenerative diseases with tau-based inclusions". Archives of Neurology. 61 (12): 1915–19. doi:10.1001/archneur.61.12.1915. PMID 15596612.
  4. ^ Lewy, Friedrich. "Whonamedit?".
  5. ^ Hake MD, Ann Marie. "Dementia with Lewy bodies". MEDMERITS TM. Archived from the original on 2016-07-04.
  6. ^ a b c d Engelhardt E (October 2017). "Lafora and Trétiakoff: the naming of the inclusion bodies discovered by Lewy". Arquivos de Neuro-Psiquiatria (Historical article). 75 (10): 751–53. doi:10.1590/0004-282X20170116. PMID 29166468.
  7. ^ Engelhardt E, Gomes MD (2017). "Lewy and his inclusion bodies: Discovery and rejection". Dementia & Neuropsychologia. 11 (2): 198–201. doi:10.1590/1980-57642016dn11-020012. PMC 5710688. PMID 29213511.
  8. ^ García-Albea E, Pérez Trullen JM (December 2003). "The Spanish school of neurology and the first American cases of Alzheimer's disease". Journal of the History of the Neurosciences. 12 (4): 437–45. doi:10.1076/jhin.12.4.437.27919. PMID 15069873.
  9. ^ Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E (March–April 2003). "Staging of brain pathology related to sporadic Parkinson's disease". Neurobiology of Aging. 24 (2): 197–211. doi:10.1016/S0197-4580(02)00065-9. PMID 12498954.
  10. ^ Engelender S (April 2008). "Ubiquitination of alpha-synuclein and autophagy in Parkinson's disease". Autophagy. 4 (3): 372–74. doi:10.4161/auto.5604. PMID 18216494.
  11. ^ Ishizawa T, Mattila P, Davies P, Wang D, Dickson DW (April 2003). "Colocalization of tau and alpha-synuclein epitopes in Lewy bodies". Journal of Neuropathology and Experimental Neurology. 62 (4): 389–97. doi:10.1093/jnen/62.4.389. PMID 12722831.
  12. ^ Arima K, Hirai S, Sunohara N, Aoto K, Izumiyama Y, Uéda K, Ikeda K, Kawai M (October 1999). "Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies". Brain Research. 843 (1–2): 53–61. doi:10.1016/S0006-8993(99)01848-X. PMID 10528110.
  13. ^ Schmidt ML, Martin JA, Lee VM, Trojanowski JQ (1996). "Convergence of Lewy bodies and neurofibrillary tangles in amygdala neurons of Alzheimer's disease and Lewy body disorders". Acta Neuropathologica. 91 (5): 475–81. doi:10.1007/s004010050454. PMID 8740227.
  14. ^ Tanaka M, Kim YM, Lee G, Junn E, Iwatsubo T, Mouradian MM (February 2004). "Aggresomes formed by alpha-synuclein and synphilin-1 are cytoprotective". The Journal of Biological Chemistry. 279 (6): 4625–31. doi:10.1074/jbc.M310994200. PMID 14627698.
  15. ^ Schaser AJ, Osterberg VR, Dent SE, Stackhouse TL, Wakeham CM, Boutros SW, Weston LJ, Owen N, Weissman TA, Luna E, Raber J, Luk KC, McCullough AK, Woltjer RL, Unni VK. "Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders". Sci Rep. 2019 Jul 29;9(1):10919. PMID 31358782 PMC PMC6662836 doi:10.1038/s41598-019-47227-z
  16. ^ Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (May 1998). "alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies". Proceedings of the National Academy of Sciences of the United States of America. 95 (11): 6469–73. Bibcode:1998PNAS...95.6469G. doi:10.1073/pnas.95.11.6469. PMC 27806. PMID 9600990.
  17. ^ a b Marui W, Iseki E, Kato M, Akatsu H, Kosaka K (August 2004). "Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease". Acta Neuropathologica. 108 (2): 121–28. doi:10.1007/s00401-004-0869-4. PMID 15235805.
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