lewy bodies

Summary

Summary: Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of Lewy bodies is the histological marker of the degenerative changes in LEWY BODY DISEASE and PARKINSON DISEASE but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex.

Top Publications

  1. Johnson M, Ekonomou A, Hobbs C, Ballard C, Perry R, Perry E. Neurogenic marker abnormalities in the hippocampus in dementia with Lewy bodies. Hippocampus. 2011;21:1126-36 pubmed publisher
    Dementia with Lewy bodies (DLB) is associated with alpha synuclein pathology and slowly progressive dementia. Progenitor abnormalities have previously been reported in the subventricular zone (SVZ) adjacent to the lateral ventricle...
  2. Wilson R, Yu L, Schneider J, Arnold S, Buchman A, Bennett D. Lewy bodies and olfactory dysfunction in old age. Chem Senses. 2011;36:367-73 pubmed publisher
    ..b>Lewy bodies were identified with antibodies to alpha-synuclein and classified as nigral, limbic, or neocortical based on ..
  3. Bhak G, Lee J, Hahn J, Paik S. Granular assembly of alpha-synuclein leading to the accelerated amyloid fibril formation with shear stress. PLoS ONE. 2009;4:e4177 pubmed publisher
  4. Ikemura M, Saito Y, Sengoku R, Sakiyama Y, Hatsuta H, Kanemaru K, et al. Lewy body pathology involves cutaneous nerves. J Neuropathol Exp Neurol. 2008;67:945-53 pubmed publisher
    ..We demonstrate for the first time that the skin is involved and may be a highly specific and useful biopsy site for the pathological diagnosis of LB diseases. ..
  5. Folgoas E, Lebouvier T, Leclair Visonneau L, Cersosimo M, Barthelaix A, Derkinderen P, et al. Diagnostic value of minor salivary glands biopsy for the detection of Lewy pathology. Neurosci Lett. 2013;551:62-4 pubmed publisher
    ..Two control subjects exhibited weak phosphorylated alpha-synuclein immunoreactivity. Our results do not support the use of minor salivary glands biopsy for the detection of Lewy pathology in living subjects. ..
  6. Paisán Ruiz C, Li A, Schneider S, Holton J, Johnson R, Kidd D, et al. Widespread Lewy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations. Neurobiol Aging. 2012;33:814-23 pubmed publisher
    ..Later onset cases tended to have less tau involvement but still severe alpha-synuclein pathology. The clinical and neuropathological features clearly represent a link between PLA2G6 and parkinsonian disorders. ..
  7. Jellinger K. Formation and development of Lewy pathology: a critical update. J Neurol. 2009;256 Suppl 3:270-9 pubmed publisher
    Filamentous protein inclusions in neurons (Lewy bodies, LB) and dystrophic neurites containing pathologic alpha-synuclein (alpha Syn) are the morphologic hallmarks of sporadic Parkinson disease (PD) and dementia with Lewy bodies (DLB), ..
  8. Brundin P, Li J, Holton J, Lindvall O, Revesz T. Research in motion: the enigma of Parkinson's disease pathology spread. Nat Rev Neurosci. 2008;9:741-5 pubmed publisher
    ..According to these studies, implanted neurons developed alpha-synuclein- and ubiquitin-positive Lewy bodies more than a decade after transplantation...
  9. Redeker V, Pemberton S, Bienvenut W, Bousset L, Melki R. Identification of protein interfaces between ?-synuclein, the principal component of Lewy bodies in Parkinson disease, and the molecular chaperones human Hsc70 and the yeast Ssa1p. J Biol Chem. 2012;287:32630-9 pubmed
    Fibrillar ?-synuclein (?-Syn) is the principal component of Lewy bodies, which are evident in individuals affected by Parkinson disease (PD)...

More Information

Publications62

  1. Zaccai J, Brayne C, McKeith I, Matthews F, Ince P. Patterns and stages of alpha-synucleinopathy: Relevance in a population-based cohort. Neurology. 2008;70:1042-8 pubmed publisher
    ..Seventy-six brains showed Lewy bodies. Half (51%) conformed to the Braak hypothesis while 17% had pathology in a higher region which was absent in a ..
  2. Olanow C, McNaught K. Parkinson's disease, proteins, and prions: milestones. Mov Disord. 2011;26:1056-71 pubmed publisher
    Parkinson's disease (PD) is characterized by protein accumulation in the form of Lewy bodies and neurites...
  3. Anderson L, Betarbet R, Gearing M, Gulcher J, Hicks A, Stefansson K, et al. PARK10 candidate RNF11 is expressed by vulnerable neurons and localizes to Lewy bodies in Parkinson disease brain. J Neuropathol Exp Neurol. 2007;66:955-64 pubmed
    ..Moreover, RNF11 is expressed by vulnerable neurons of the substantia nigra and sequestered into Lewy bodies in brains of patients with idiopathic PD...
  4. Fronczek R, Overeem S, Lee S, Hegeman I, van Pelt J, van Duinen S, et al. Hypocretin (orexin) loss in Parkinson's disease. Brain. 2007;130:1577-85 pubmed
    ..Furthermore, presence of Lewy bodies was verified in the hypothalamic hypocretin cell area. Data are presented as median (25th-75th percentile)...
  5. Burke R, Dauer W, Vonsattel J. A critical evaluation of the Braak staging scheme for Parkinson's disease. Ann Neurol. 2008;64:485-91 pubmed publisher
    ..the patterns of synucleinopathy that Braak described are often not observed, particularly in dementia with Lewy bodies and when synucleinopathy occurs in the absence of neurological manifestations...
  6. Greffard S, Verny M, Bonnet A, Seilhean D, Hauw J, Duyckaerts C. A stable proportion of Lewy body bearing neurons in the substantia nigra suggests a model in which the Lewy body causes neuronal death. Neurobiol Aging. 2010;31:99-103 pubmed publisher
    b>Lewy bodies in Parkinson disease could be innocent bystanders or active agents responsible for neuronal death...
  7. Uversky V. Neuropathology, biochemistry, and biophysics of alpha-synuclein aggregation. J Neurochem. 2007;103:17-37 pubmed
    ..These diseases, known as synucleinopathies, include Parkinson's disease, dementia with Lewy bodies (LBs), diffuse LB disease, the LB variant of Alzheimer's disease, multiple system atrophy, and ..
  8. Kordower J, Dodiya H, Kordower A, TERPSTRA B, Paumier K, Madhavan L, et al. Transfer of host-derived ? synuclein to grafted dopaminergic neurons in rat. Neurobiol Dis. 2011;43:552-7 pubmed publisher
    Multiple laboratories have recently demonstrated that long-term dopaminergic transplants form Lewy bodies in patients with Parkinson's disease...
  9. Kingsbury A, Bandopadhyay R, Silveira Moriyama L, Ayling H, Kallis C, Sterlacci W, et al. Brain stem pathology in Parkinson's disease: an evaluation of the Braak staging model. Mov Disord. 2010;25:2508-15 pubmed publisher
    ..These findings broadly support the Braak hypothesis of caudo-rostral development but indicate that the extent of the disease in the cortex and the severity of pathology in the medulla were independent of one another. ..
  10. Wei J, Fujita M, Nakai M, Waragai M, Watabe K, Akatsu H, et al. Enhanced lysosomal pathology caused by beta-synuclein mutants linked to dementia with Lewy bodies. J Biol Chem. 2007;282:28904-14 pubmed
    ..V70M) of beta-synuclein (beta-syn), the homologue of alpha-syn, have been recently identified in dementia with Lewy bodies. However, the mechanism through which these mutations influence the pathogenesis of dementia with Lewy bodies ..
  11. Nelson P, Jicha G, Kryscio R, Abner E, Schmitt F, Cooper G, et al. Low sensitivity in clinical diagnoses of dementia with Lewy bodies. J Neurol. 2010;257:359-66 pubmed publisher
    ..This was particularly true in the case of dementia with Lewy bodies (DLB): the sensitivity of clinical diagnoses was quite low (32.1% for pure DLB and 12...
  12. Devine M, Lewis P. Emerging pathways in genetic Parkinson's disease: tangles, Lewy bodies and LRRK2. FEBS J. 2008;275:5748-57 pubmed publisher
    ..This minireview explores this model, in the context of our current understanding of the biochemistry of LRRK2, alpha-synuclein and tau. ..
  13. Colloby S, Taylor J, Davison C, Lloyd J, Firbank M, McKeith I, et al. Multivariate spatial covariance analysis of 99mTc-exametazime SPECT images in dementia with Lewy bodies and Alzheimer's disease: utility in differential diagnosis. J Cereb Blood Flow Metab. 2013;33:612-8 pubmed publisher
    ..a spatial covariance analysis (SCA) approach to assess its diagnostic value in distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease (AD)...
  14. Kokoulina P, Rohn T. Caspase-cleaved transactivation response DNA-binding protein 43 in Parkinson's disease and dementia with Lewy bodies. Neurodegener Dis. 2010;7:243-50 pubmed publisher
    ..proteolytic modifications of TDP-43 are a relevant finding in Parkinson's disease (PD) and dementia with Lewy bodies (DLB)...
  15. Sengoku R, Saito Y, Ikemura M, Hatsuta H, Sakiyama Y, Kanemaru K, et al. Incidence and extent of Lewy body-related alpha-synucleinopathy in aging human olfactory bulb. J Neuropathol Exp Neurol. 2008;67:1072-83 pubmed publisher
    ..In 5 patients, Lewy bodies were found only in the OB by hematoxylin and eosin stain; 3 of these patients had Alzheimer disease, and all ..
  16. Angot E, Steiner J, Hansen C, Li J, Brundin P. Are synucleinopathies prion-like disorders?. Lancet Neurol. 2010;9:1128-38 pubmed publisher
    A shared neuropathological feature of idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy is the development of intracellular aggregates of ?-synuclein that gradually engage increasing parts of the ..
  17. Obi K, Akiyama H, Kondo H, Shimomura Y, Hasegawa M, Iwatsubo T, et al. Relationship of phosphorylated alpha-synuclein and tau accumulation to Abeta deposition in the cerebral cortex of dementia with Lewy bodies. Exp Neurol. 2008;210:409-20 pubmed publisher
    Alpha-synuclein accumulated in the brain of dementia with Lewy bodies (DLB) is phosphorylated at serine129 (palpha-synuclein)...
  18. Szargel R, Rott R, Engelender S. Synphilin-1 isoforms in Parkinson's disease: regulation by phosphorylation and ubiquitylation. Cell Mol Life Sci. 2008;65:80-8 pubmed
    Parkinson's disease (PD) is characterized by the death of dopaminergic neurons and the presence of Lewy bodies in the substantia nigra pars compacta...
  19. Hindle J. Ageing, neurodegeneration and Parkinson's disease. Age Ageing. 2010;39:156-61 pubmed publisher
    ..The formation of Lewy bodies may represent a marker for protective mechanisms against age-related dysfunction and degeneration of the ..
  20. Zucchelli S, Codrich M, Marcuzzi F, Pinto M, Vilotti S, Biagioli M, et al. TRAF6 promotes atypical ubiquitination of mutant DJ-1 and alpha-synuclein and is localized to Lewy bodies in sporadic Parkinson's disease brains. Hum Mol Genet. 2010;19:3759-70 pubmed publisher
    ..Nigra and the formation of ubiquitin- and alpha-synuclein (aSYN)-positive cytoplasmic inclusions called Lewy bodies (LBs). Although most PD cases are sporadic, families with genetic mutations have been found...
  21. Mrak R. Neuropathology and the neuroinflammation idea. J Alzheimers Dis. 2009;18:473-81 pubmed publisher
    ..Further observations have extended these ideas to alpha-synuclein-based diseases (Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy) as well as other neurodegenerative diseases and conditions.
  22. Fodero Tavoletti M, Smith D, McLean C, Adlard P, Barnham K, Foster L, et al. In vitro characterization of Pittsburgh compound-B binding to Lewy bodies. J Neurosci. 2007;27:10365-71 pubmed
    Dementia with Lewy bodies (DLB) is pathologically characterized by the presence of alpha-synuclein-containing Lewy bodies within the neocortical, limbic, and paralimbic regions...
  23. Luk K, Song C, O BRIEN P, Stieber A, Branch J, Brunden K, et al. Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc Natl Acad Sci U S A. 2009;106:20051-6 pubmed publisher
    Cytoplasmic inclusions containing alpha-synuclein (alpha-Syn) fibrils, referred to as Lewy bodies (LBs), are the signature neuropathological hallmarks of Parkinson's disease (PD)...
  24. Mamais A, Raja M, Manzoni C, Dihanich S, Lees A, Moore D, et al. Divergent ?-synuclein solubility and aggregation properties in G2019S LRRK2 Parkinson's disease brains with Lewy Body pathology compared to idiopathic cases. Neurobiol Dis. 2013;58:183-90 pubmed publisher
    ..This divergence in solubility is most notable in the basal ganglia, a region that is affected preclinically and is damaged before overt dopaminergic cell death. ..
  25. Kawamoto Y, Ito H, Ihara M, Takahashi R. Immunohistochemical localization of X-linked inhibitor of apoptosis protein in brainstem-type and cortical Lewy bodies. Neuroreport. 2012;23:162-7 pubmed publisher
    ..of XIAP and the relationship between XIAP and HtrA2/Omi in patients with Parkinson's disease or dementia with Lewy bodies. We conducted immunohistochemical studies on XIAP in formalin-fixed, paraffin-embedded sections from eight ..
  26. Miki Y, Mori F, Tanji K, Kakita A, Takahashi H, Wakabayashi K. Accumulation of histone deacetylase 6, an aggresome-related protein, is specific to Lewy bodies and glial cytoplasmic inclusions. Neuropathology. 2011;31:561-8 pubmed publisher
    ..Previous studies have shown that HDAC6 is concentrated in Lewy bodies (LBs) in Parkinson's disease (PD) and dementia with LBs (DLB) (Cell 115: 727-738, 2003)...
  27. Olzmann J, Li L, Chudaev M, Chen J, Perez F, Palmiter R, et al. Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6. J Cell Biol. 2007;178:1025-38 pubmed
    ..Mutations in the E3 ligase parkin cause autosomal recessive Parkinson's disease that is devoid of Lewy bodies, which are similar to aggresomes...
  28. Chu Y, Kordower J. Lewy body pathology in fetal grafts. Ann N Y Acad Sci. 2010;1184:55-67 pubmed publisher
    ..These pathological changes suggest that PD is an ongoing process that affects grafted cells in the striatum in a manner similar to how resident dopamine neurons are affected in the substantia nigra. ..
  29. Kanazawa T, Uchihara T, Takahashi A, Nakamura A, Orimo S, Mizusawa H. Three-layered structure shared between Lewy bodies and lewy neurites-three-dimensional reconstruction of triple-labeled sections. Brain Pathol. 2008;18:415-22 pubmed publisher
    b>Lewy bodies (LBs) and Lewy neurites (LNs) are the hallmarks of Parkinson's disease (PD)...
  30. Leverenz J, Umar I, Wang Q, Montine T, McMillan P, Tsuang D, et al. Proteomic identification of novel proteins in cortical lewy bodies. Brain Pathol. 2007;17:139-45 pubmed
    Lewy body (LB) inclusions are one of the pathological hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB)...
  31. Meeus B, Theuns J, Van Broeckhoven C. The genetics of dementia with Lewy bodies: what are we missing?. Arch Neurol. 2012;69:1113-8 pubmed publisher
    Dementia with Lewy bodies is a complex brain disorder and a key member of the Lewy body disease spectrum. Its genetic etiology is unclear, and information is scattered...
  32. Miki Y, Tomiyama M, Ueno T, Haga R, Nishijima H, Suzuki C, et al. Clinical availability of skin biopsy in the diagnosis of Parkinson's disease. Neurosci Lett. 2010;469:357-9 pubmed publisher
    ..The skin remains to be a promising tissue to be examined for the premortem diagnosis of PD. ..
  33. Daher J, Pletnikova O, Biskup S, Musso A, Gellhaar S, Galter D, et al. Neurodegenerative phenotypes in an A53T ?-synuclein transgenic mouse model are independent of LRRK2. Hum Mol Genet. 2012;21:2420-31 pubmed publisher
    ..Fibrillar forms of ?-synuclein are a major component of Lewy bodies, the intracytoplasmic proteinaceous inclusions that are a pathological hallmark of idiopathic and certain ..
  34. Hansen C, Angot E, Bergström A, Steiner J, Pieri L, Paul G, et al. ?-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J Clin Invest. 2011;121:715-25 pubmed publisher
    ..disease who received fetal mesencephalic transplants show that ?-synuclein-containing (?-syn-containing) Lewy bodies gradually appear in grafted neurons...
  35. Parelkar S, Cadena J, Kim C, Wang Z, Sugal R, Bentley B, et al. The parkin-like human homolog of Drosophila ariadne-1 (HHARI) can induce aggresome formation in mammalian cells and is immunologically detectable in Lewy bodies. J Mol Neurosci. 2012;46:109-21 pubmed publisher
    ..In addition, endogenous HHARI is found in human Lewy bodies in both Parkinson's disease and diffuse Lewy body disorder...
  36. Slodzinski H, Moran L, Michael G, Wang B, Novoselov S, Cheetham M, et al. Homocysteine-induced endoplasmic reticulum protein (herp) is up-regulated in parkinsonian substantia nigra and present in the core of Lewy bodies. Clin Neuropathol. 2009;28:333-43 pubmed
    ..Accumulation of Herp protein was also detected in the core of Lewy bodies suggesting a role in their formation...
  37. Duyckaerts C, Delatour B, Potier M. Classification and basic pathology of Alzheimer disease. Acta Neuropathol. 2009;118:5-36 pubmed publisher
    ..plaque only and tangle predominant), the type of onset (focal onset), the cause (genetic or sporadic) and the associated lesions (Lewy bodies, vascular lesions, hippocampal sclerosis, TDP-43 inclusions and argyrophilic grain disease).
  38. Fujishiro H, Ferman T, Boeve B, Smith G, Graff Radford N, Uitti R, et al. Validation of the neuropathologic criteria of the third consortium for dementia with Lewy bodies for prospectively diagnosed cases. J Neuropathol Exp Neurol. 2008;67:649-56 pubmed publisher
    There is limited information on the validity of the pathologic criteria of the Third Consortium on Dementia with Lewy bodies (CDLB), and none are based on prospectively diagnosed cases...
  39. Ye L, Velasco A, Fraser G, Beach T, Sue L, Osredkar T, et al. In vitro high affinity alpha-synuclein binding sites for the amyloid imaging agent PIB are not matched by binding to Lewy bodies in postmortem human brain. J Neurochem. 2008;105:1428-37 pubmed publisher
    ..was detected with amygdala sections from Parkinson's disease cases containing frequent AS-immunoreactive Lewy bodies and related neurities...
  40. Dickson D, Fujishiro H, Orr C, DelleDonne A, Josephs K, Frigerio R, et al. Neuropathology of non-motor features of Parkinson disease. Parkinsonism Relat Disord. 2009;15 Suppl 3:S1-5 pubmed publisher
    ..signs in PD are tightly linked to striatonigral dopaminergic denervation associated with neuronal loss and Lewy bodies in the residual neurons of the substantia nigra...
  41. Weisman D, Cho M, Taylor C, Adame A, Thal L, Hansen L. In dementia with Lewy bodies, Braak stage determines phenotype, not Lewy body distribution. Neurology. 2007;69:356-9 pubmed
    We used an autopsy series to determine whether the newest dementia with Lewy bodies (DLB) consensus pathologic classification correlates with premortem diagnosis of DLB...
  42. Tofaris G, Kim H, Hourez R, Jung J, Kim K, Goldberg A. Ubiquitin ligase Nedd4 promotes alpha-synuclein degradation by the endosomal-lysosomal pathway. Proc Natl Acad Sci U S A. 2011;108:17004-9 pubmed publisher
    ..human brains, Nedd4 is present in pigmented neurons and is expressed especially strongly in neurons containing Lewy bodies. Thus, ubiquitination by Nedd4 targets ?-synuclein to the endosomal-lysosomal pathway and, by reducing ?-..
  43. Tofaris G, Revesz T, Jacques T, Papacostas S, Chataway J. Adult-onset neurodegeneration with brain iron accumulation and cortical alpha-synuclein and tau pathology: a distinct clinicopathological entity. Arch Neurol. 2007;64:280-2 pubmed
    ..Cortical biopsy revealed Lewy bodies with predominant alpha-synuclein and less extensive tau-positive neurites...
  44. Li J, Englund E, Holton J, Soulet D, Hagell P, Lees A, et al. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med. 2008;14:501-3 pubmed publisher
    ..of transplanted fetal mesencephalic dopaminergic neurons (11-16 years) developed alpha-synuclein-positive Lewy bodies in grafted neurons...
  45. Beyer K, Ariza A. ?-Synuclein posttranslational modification and alternative splicing as a trigger for neurodegeneration. Mol Neurobiol. 2013;47:509-24 pubmed publisher
    Lewy body diseases include Parkinson disease and dementia with Lewy bodies and are characterized by the widespread distribution of Lewy bodies in virtually every brain area. The main component of Lewy bodies is alpha-synuclein (AS)...
  46. Halliday G, Herrero M, Murphy K, McCann H, Ros Bernal F, Barcia C, et al. No Lewy pathology in monkeys with over 10 years of severe MPTP Parkinsonism. Mov Disord. 2009;24:1519-23 pubmed publisher
    ..This suggests that MPTP-induced oxidative stress and inflammation per se are not sufficient for Lewy body formation, or Lewy bodies are human specific.
  47. Beyer M, Larsen J, Aarsland D. Gray matter atrophy in Parkinson disease with dementia and dementia with Lewy bodies. Neurology. 2007;69:747-54 pubmed
    The nosologic relationship between dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) is continuously being debated...
  48. Moran L, Hickey L, Michael G, Derkacs M, Christian L, Kalaitzakis M, et al. Neuronal pentraxin II is highly upregulated in Parkinson's disease and a novel component of Lewy bodies. Acta Neuropathol. 2008;115:471-8 pubmed
    ..We show here that it is a novel component of Lewy bodies and Lewy neurites in sporadic Parkinson's disease (PD)...
  49. Marx F, Soehn A, Berg D, Melle C, Schiesling C, Lang M, et al. The proteasomal subunit S6 ATPase is a novel synphilin-1 interacting protein--implications for Parkinson's disease. FASEB J. 2007;21:1759-67 pubmed
    ..protein and substrate of the ubiquitin E3 ligase Parkin (PARK2) and because of its presence in Lewy bodies (LB) in brains of PD patients...
  50. Devine M, Gwinn K, Singleton A, Hardy J. Parkinson's disease and α-synuclein expression. Mov Disord. 2011;26:2160-8 pubmed publisher
    ..linked to Parkinson's disease, and is arguably the most important: the protein is the principal constituent of Lewy bodies, and variation at its locus is the major genetic risk factor for sporadic disease...
  51. Engelender S. Ubiquitination of alpha-synuclein and autophagy in Parkinson's disease. Autophagy. 2008;4:372-4 pubmed
    alpha-Synuclein is mutated in Parkinson's disease (PD) and is found in cytosolic inclusions, called Lewy bodies, in sporadic forms of the disease...
  52. Jellinger K. Neuropathology of sporadic Parkinson's disease: evaluation and changes of concepts. Mov Disord. 2012;27:8-30 pubmed publisher
    ..the central, peripheral and autonomic nervous system and other organs associated with widespread occurrence of Lewy bodies and dystrophic Lewy neurites...
  53. Kanazawa T, Adachi E, Orimo S, Nakamura A, Mizusawa H, Uchihara T. Pale neurites, premature ?-synuclein aggregates with centripetal extension from axon collaterals. Brain Pathol. 2012;22:67-78 pubmed publisher
    ..This branching-oriented extension of ?S is related to its selective predisposition to systems with highly divergent axons, preferentially affected in PD, which may explain barely somatotopic manifestations of PD. ..