Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388(6645):839–840. doi:10.1038/42166.
Article
CAS
PubMed
Google Scholar
Orimo S, Uchihara T, Nakamura A, Mori F, Kakita A, Wakabayashi K, Takahashi H (2008) Axonal alpha-synuclein aggregates herald centripetal degeneration of cardiac sympathetic nerve in Parkinson’s disease. Brain 131(Pt 3):642–650. doi:10.1093/brain/awm302.
Article
PubMed
Google Scholar
Beach TG, Adler CH, Sue LI, Vedders L, Lue L, White Iii CL, Akiyama H, Caviness JN, Shill HA, Sabbagh MN, Walker DG, Arizona Parkinson’s Disease C (2010) Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 119(6):689–702. doi:10.1007/s00401-010-0664-3.
Article
PubMed Central
CAS
PubMed
Google Scholar
Wakabayashi K, Mori F, Tanji K, Orimo S, Takahashi H (2010) Involvement of the peripheral nervous system in synucleinopathies, tauopathies and other neurodegenerative proteinopathies of the brain. Acta Neuropathol 120(1):1–12. doi:10.1007/s00401-010-0706-x.
Article
PubMed
Google Scholar
Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW (2008) Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat Med 14(5):504–506. doi:10.1038/nm1747.
Article
CAS
PubMed
Google Scholar
Li JY, Englund E, Holton JL, Soulet D, Hagell P, Lees AJ, Lashley T, Quinn NP, Rehncrona S, Bjorklund A, Widner H, Revesz T, Lindvall O, Brundin P (2008) Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med 14(5):501–503. doi:10.1038/nm1746
Article
CAS
PubMed
Google Scholar
Masuda-Suzukake M, Nonaka T, Hosokawa M, Oikawa T, Arai T, Akiyama H, Mann DM, Hasegawa M (2013) Prion-like spreading of pathological alpha-synuclein in brain. Brain 136(Pt 4):1128–1138. doi:10.1093/brain/awt037.
Article
PubMed Central
PubMed
Google Scholar
Brundin P, Li JY, Holton JL, Lindvall O, Revesz T (2008) Research in motion: the enigma of Parkinson’s disease pathology spread. Nat Rev Neurosci 9(10):741–745. doi:10.1038/nrn2477.
Article
CAS
PubMed
Google Scholar
Goedert M, Clavaguera F, Tolnay M (2010) The propagation of prion-like protein inclusions in neurodegenerative diseases. Trends Neurosci 33(7):317–325. doi:10.1016/j.tins.2010.04.003.
Article
CAS
PubMed
Google Scholar
Luk KC, Kehm VM, Zhang B, O’Brien P, Trojanowski JQ, Lee VM (2012) Intracerebral inoculation of pathological alpha-synuclein initiates a rapidly progressive neurodegenerative alpha-synucleinopathy in mice. J Exp Med 209(5):975–986. doi:10.1084/jem.20112457.
Article
PubMed Central
CAS
PubMed
Google Scholar
Mougenot AL, Nicot S, Bencsik A, Morignat E, Verchere J, Lakhdar L, Legastelois S, Baron T (2012) Prion-like acceleration of a synucleinopathy in a transgenic mouse model. Neurobiol Aging 33(9):2225–2228. doi:10.1016/j.neurobiolaging.2011.06.022.
Article
CAS
PubMed
Google Scholar
Olanow CW, Prusiner SB (2009) Is Parkinson’s disease a prion disorder? Proc Natl Acad Sci U S A 106(31):12571–12572. doi:10.1073/pnas.0906759106.
Article
PubMed Central
CAS
PubMed
Google Scholar
Luk KC, Kehm V, Carroll J, Zhang B, O’Brien P, Trojanowski JQ, Lee VM (2012) Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338(6109):949–953. doi:10.1126/science.1227157.
Article
PubMed Central
CAS
PubMed
Google Scholar
Desplats P, Lee HJ, Bae EJ, Patrick C, Rockenstein E, Crews L, Spencer B, Masliah E, Lee SJ (2009) Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci U S A 106(31):13010–13015. doi:10.1073/pnas.0903691106.
Article
PubMed Central
CAS
PubMed
Google Scholar
Pan-Montojo F, Anichtchik O, Dening Y, Knels L, Pursche S, Jung R, Jackson S, Gille G, Spillantini MG, Reichmann H, Funk RH (2010) Progression of Parkinson’s disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS One 5(1):e8762. doi:10.1371/journal.pone.0008762.
Article
PubMed Central
PubMed
Google Scholar
Hawkes CH, Del Tredici K, Braak H (2007) Parkinson’s disease: a dual-hit hypothesis. Neuropathol Appl Neurobiol 33(6):599–614. doi:10.1111/j.1365-2990.2007.00874.x.
Article
CAS
PubMed
Google Scholar
Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24(2):197–211.
Article
PubMed
Google Scholar
Sengoku R, Saito Y, Ikemura M, Hatsuta H, Sakiyama Y, Kanemaru K, Arai T, Sawabe M, Tanaka N, Mochizuki H, Inoue K, Murayama S (2008) Incidence and extent of Lewy body-related alpha-synucleinopathy in aging human olfactory bulb. J Neuropathol Exp Neurol 67(11):1072–1083. doi:10.1097/NEN.0b013e31818b4126.
Article
PubMed
Google Scholar
Zaccai J, Brayne C, McKeith I, Matthews F, Ince PG (2008) Patterns and stages of alpha-synucleinopathy: relevance in a population-based cohort. Neurology 70(13):1042–1048. doi:10.1212/01.wnl.0000306697.48738.b6.
Article
CAS
PubMed
Google Scholar
Del Tredici K, Braak H (2012) Spinal cord lesions in sporadic Parkinson’s disease. Acta Neuropathol 124(5):643–664. doi:10.1007/s00401-012-1028-y.
Article
PubMed
Google Scholar
Braak H, Sastre M, Bohl JR, de Vos RA, Del Tredici K (2007) Parkinson’s disease: lesions in dorsal horn layer I, involvement of parasympathetic and sympathetic pre- and postganglionic neurons. Acta Neuropathol 113(4):421–429. doi:10.1007/s00401-007-0193-x.
Article
PubMed
Google Scholar
Tamura T, Yoshida M, Hashizume Y, Sobue G (2012) Lewy body-related alpha-synucleinopathy in the spinal cord of cases with incidental Lewy body disease. Neuropathology 32(1):13–22. doi:10.1111/j.1440-1789.2011.01211.x.
Article
PubMed
Google Scholar
Bowsher D (1957) Termination of the central pain pathway in man: the conscious appreciation of pain. Brain 80(4):606–622.
Article
CAS
PubMed
Google Scholar
Kojima M, Sano Y (1983) The organization of serotonin fibers in the anterior column of the mammalian spinal cord. An immunohistochemical study. Anat Embryol (Berl) 167(1):1–11.
Article
CAS
Google Scholar
Westlund KN, Bowker RM, Ziegler MG, Coulter JD (1982) Descending noradrenergic projections and their spinal terminations. Prog Brain Res 57:219–238. doi:10.1016/s0079-6123(08)64131-x.
Article
CAS
PubMed
Google Scholar
Sah P, Faber ES, Lopez De Armentia M, Power J (2003) The amygdaloid complex: anatomy and physiology. Physiol Rev 83(3):803–834. doi:10.1152/physrev.00002.2003.
Article
CAS
PubMed
Google Scholar
McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65(12):1863–1872. doi:10.1212/01.wnl.0000187889.17253.b1.
Article
CAS
PubMed
Google Scholar
Saito Y, Ruberu NN, Sawabe M, Arai T, Kazama H, Hosoi T, Yamanouchi H, Murayama S (2004) Lewy body-related alpha-synucleinopathy in aging. J Neuropathol Exp Neurol 63(7):742–749.
PubMed
Google Scholar
Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82(4):239–259.
Article
CAS
PubMed
Google Scholar
Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L (1991) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41(4):479–486.
Article
CAS
PubMed
Google Scholar
Thal DR, Rub U, Orantes M, Braak H (2002) Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58(12):1791–1800.
Article
PubMed
Google Scholar
Saito Y, Ruberu NN, Sawabe M, Arai T, Tanaka N, Kakuta Y, Yamanouchi H, Murayama S (2004) Staging of argyrophilic grains: an age-associated tauopathy. J Neuropathol Exp Neurol 63(9):911–918.
PubMed
Google Scholar
Lerner A, Bagic A (2008) Olfactory pathogenesis of idiopathic Parkinson disease revisited. Mov Disord 23(8):1076–1084. doi:10.1002/mds.22066.
Article
PubMed
Google Scholar
Zemlan FP, Behbehani MM, Beckstead RM (1984) Ascending and descending projections from nucleus reticularis magnocellularis and nucleus reticularis gigantocellularis: an autoradiographic and horseradish peroxidase study in the rat. Brain Res 292(2):207–220.
Article
CAS
PubMed
Google Scholar
Marui W, Iseki E, Nakai T, Miura S, Kato M, Ueda K, Kosaka K (2002) Progression and staging of Lewy pathology in brains from patients with dementia with Lewy bodies. J Neurol Sci 195(2):153–159.
Article
PubMed
Google Scholar
Wakabayashi K, Hayashi S, Kakita A, Yamada M, Toyoshima Y, Yoshimoto M, Takahashi H (1998) Accumulation of alpha-synuclein/NACP is a cytopathological feature common to Lewy body disease and multiple system atrophy. Acta Neuropathol 96(5):445–452.
Article
CAS
PubMed
Google Scholar
Wakabayashi K, Tanji K, Mori F, Takahashi H (2007) The Lewy body in Parkinson’s disease: Molecules implicated in the formation and degradation of α-synuclein aggregates. Neuropathology 27(5):494–506. doi:10.1111/j.1440-1789.2007.00803.x.
Article
PubMed
Google Scholar
Saito Y, Kawashima A, Ruberu NN, Fujiwara H, Koyama S, Sawabe M, Arai T, Nagura H, Yamanouchi H, Hasegawa M, Iwatsubo T, Murayama S (2003) Accumulation of phosphorylated alpha-synuclein in aging human brain. J Neuropathol Exp Neurol 62(6):644–654.
CAS
PubMed
Google Scholar
Braak H, Sandmann-Keil D, Gai W, Braak E (1999) Extensive axonal Lewy neurites in Parkinson’s disease: a novel pathological feature revealed by alpha-synuclein immunocytochemistry. Neurosci Lett 265(1):67–69.
Article
CAS
PubMed
Google Scholar
Holmqvist S, Chutna O, Bousset L, Aldrin-Kirk P, Li W, Bjorklund T, Wang ZY, Roybon L, Melki R, Li JY (2014) Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol 128(6):805–820. doi:10.1007/s00401-014-1343-6.
Article
PubMed
Google Scholar
Recasens A, Dehay B, Bove J, Carballo-Carbajal I, Dovero S, Perez-Villalba A, Fernagut PO, Blesa J, Parent A, Perier C, Farinas I, Obeso JA, Bezard E, Vila M (2014) Lewy body extracts from Parkinson disease brains trigger alpha-synuclein pathology and neurodegeneration in mice and monkeys. Ann Neurol 75(3):351–362. doi:10.1002/ana.24066.
Article
CAS
PubMed
Google Scholar
Rey NL, Petit GH, Bousset L, Melki R, Brundin P (2013) Transfer of human alpha-synuclein from the olfactory bulb to interconnected brain regions in mice. Acta Neuropathol 126(4):555–573. doi:10.1007/s00401-013-1160-3.
Article
PubMed Central
CAS
PubMed
Google Scholar
Donadio V, Incensi A, Leta V, Giannoccaro MP, Scaglione C, Martinelli P, Capellari S, Avoni P, Baruzzi A, Liguori R (2014) Skin nerve alpha-synuclein deposits: a biomarker for idiopathic Parkinson disease. Neurology 82(15):1362–1369. doi:10.1212/wnl.0000000000000316.
Article
CAS
PubMed
Google Scholar
Nolano M, Provitera V, Estraneo A, Selim MM, Caporaso G, Stancanelli A, Saltalamacchia AM, Lanzillo B, Santoro L (2008) Sensory deficit in Parkinson’s disease: evidence of a cutaneous denervation. Brain 131(Pt 7):1903–1911. doi:10.1093/brain/awn102.
Article
PubMed
Google Scholar
Doppler K, Ebert S, Uceyler N, Trenkwalder C, Ebentheuer J, Volkmann J, Sommer C (2014) Cutaneous neuropathy in Parkinson’s disease: a window into brain pathology. Acta Neuropathol 128(1):99–109. doi:10.1007/s00401-014-1284-0.
Article
PubMed Central
CAS
PubMed
Google Scholar
Defazio G, Berardelli A, Fabbrini G, Martino D, Fincati E, Fiaschi A, Moretto G, Abbruzzese G, Marchese R, Bonuccelli U, Del Dotto P, Barone P, De Vivo E, Albanese A, Antonini A, Canesi M, Lopiano L, Zibetti M, Nappi G, Martignoni E, Lamberti P, Tinazzi M (2008) Pain as a nonmotor symptom of Parkinson disease: evidence from a case–control study. Arch Neurol 65(9):1191–1194. doi:10.1001/archneurol.2008.2.
Article
PubMed
Google Scholar
Beiske AG, Loge JH, Ronningen A, Svensson E (2009) Pain in Parkinson’s disease: prevalence and characteristics. Pain 141(1–2):173–177. doi:10.1016/j.pain.2008.12.004.
Article
CAS
PubMed
Google Scholar
Goetz CG, Tanner CM, Levy M, Wilson RS, Garron DC (1986) Pain in Parkinson’s disease. Mov Disord 1(1):45–49. doi:10.1002/mds.870010106.
Article
CAS
PubMed
Google Scholar
Negre-Pages L, Regragui W, Bouhassira D, Grandjean H, Rascol O, DoPaMi PSG (2008) Chronic pain in Parkinson’s disease: the cross-sectional French DoPaMiP survey. Mov Disord 23(10):1361–1369. doi:10.1002/mds.22142.
Article
PubMed
Google Scholar
Caviness JN, Smith BE, Stevens JC, Adler CH, Caselli RJ, Reiners CA, Hentz JG, Muenter MD (2000) Motor unit changes in sporadic idiopathic Parkinson’s disease. Mov Disord 15(2):238–243.
Article
CAS
PubMed
Google Scholar
Caviness JN, Smith BE, Clarke Stevens J, Adler CH, Caselli RJ, Hentz JG, Manfred MS, Muenter D (2002) Motor unit number estimates in idiopathic Parkinson’s disease. Parkinsonism Relat Disord 8(3):161–164.
Article
CAS
PubMed
Google Scholar
Sacino AN, Brooks M, Thomas MA, McKinney AB, Lee S, Regenhardt RW, McGarvey NH, Ayers JI, Notterpek L, Borchelt DR, Golde TE, Giasson BI (2014) Intramuscular injection of alpha-synuclein induces CNS alpha-synuclein pathology and a rapid-onset motor phenotype in transgenic mice. Proc Natl Acad Sci U S A 111(29):10732–10737. doi:10.1073/pnas.1321785111.
Article
PubMed Central
CAS
PubMed
Google Scholar
Lebouvier T, Chaumette T, Damier P, Coron E, Touchefeu Y, Vrignaud S, Naveilhan P, Galmiche JP, Bruley des Varannes S, Derkinderen P, Neunlist M (2008) Pathological lesions in colonic biopsies during Parkinson’s disease. Gut 57(12):1741–1743. doi:10.1136/gut.2008.162503.
Article
CAS
PubMed
Google Scholar
Kuo YM, Li Z, Jiao Y, Gaborit N, Pani AK, Orrison BM, Bruneau BG, Giasson BI, Smeyne RJ, Gershon MD, Nussbaum RL (2010) Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated alpha-synuclein gene mutations precede central nervous system changes. Hum Mol Genet 19(9):1633–1650. doi:10.1093/hmg/ddq038.
Article
PubMed Central
CAS
PubMed
Google Scholar
Abbott RD, Petrovitch H, White LR, Masaki KH, Tanner CM, Curb JD, Grandinetti A, Blanchette PL, Popper JS, Ross GW (2001) Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology 57(3):456–462.
Article
CAS
PubMed
Google Scholar
Braak H, de Vos RA, Bohl J, Del Tredici K (2006) Gastric alpha-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neurosci Lett 396(1):67–72. doi:10.1016/j.neulet.2005.11.012.
Article
CAS
PubMed
Google Scholar
Pan-Montojo F, Schwarz M, Winkler C, Arnhold M, O’Sullivan GA, Pal A, Said J, Marsico G, Verbavatz JM, Rodrigo-Angulo M, Gille G, Funk RH, Reichmann H (2012) Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Sci Rep 2:898. doi:10.1038/srep00898.
Article
PubMed Central
PubMed
Google Scholar