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Is Braak staging valid for all types of Parkinson’s disease?

  • Neurology and Preclinical Neurological Studies - Review Article
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Abstract

Braak et al. proposed that cases with Lewy pathology in the peripheral nervous sytem, spinal cord and brain stem are prodromal Parkinson’s disease (PD), suggesting a hypothesized progression of PD pathology. However, the putative potential of peripheral α-synuclein to promote brain pathology has been questioned recently. The Braak staging is a matter of vigorous debate, since < 100% of cases with Lewy pathology fitting the proposed PD staging scheme; however, most studies assessing typical PD cases show that the vast majority (80–100%) fit the Braak staging scheme. Incidental Lewy body disease and PD can show Lewy pathology in substantia nigra or other brain areas without involvement of dorsal motor nucleus of the vagus nerve. The Braak staging system is valid for PD patients with young onset, long duration with motor symptoms, but not for others, e.g., late onset and rapid course PD. The validity of Braak staging and its relationship to various subtypes of PD warrants further studies.

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References

  • Aho L, Parkkinen L, Pirttila T, Alafuzoff I (2008) Systematic appraisal using immunohistochemistry of brain pathology in aged and demented subjects. Dement Geriatr Cogn Disord 25:423–432

    Article  CAS  PubMed  Google Scholar 

  • Alafuzoff I, Ince PG, Arzberger T, Al-Sarraj S, Bell J, Bodi I, Bogdanovic N, Bugiani O, Ferrer I, Gelpi E, Gentleman S, Giaccone G, Ironside JW, Kavantzas N, King A, Korkolopoulou P, Kovacs GG, Meyronet D, Monoranu C, Parchi P, Parkkinen L, Patsouris E, Roggendorf W, Rozemuller A, Stadelmann-Nessler C, Streichenberger N, Thal DR, Kretzschmar H (2009) Staging/typing of Lewy body related alpha-synuclein pathology: a study of the BrainNet Europe Consortium. Acta Neuropathol 117:635–652

    Article  CAS  PubMed  Google Scholar 

  • Attems J, Jellinger KA (2008) The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson’s disease. Neuropathol Appl Neurobiol 34:466–467

    Article  CAS  PubMed  Google Scholar 

  • Barker RA, Williams-Gray CH (2016) Review: the spectrum of clinical features seen with alpha synuclein pathology. Neuropathol Appl Neurobiol 42:6–19

    Article  CAS  PubMed  Google Scholar 

  • Beach TG, Adler CH, Sue LI, Peirce JB, Bachalakuri J, Dalsing-Hernandez JE, Lue LF, Caviness JN, Connor DJ, Sabbagh MN, Walker DG (2008) Reduced striatal tyrosine hydroxylase in incidental Lewy body disease. Acta Neuropathol 115:445–451

    Article  CAS  PubMed  Google Scholar 

  • Beach TG, Adler CH, Lue L, Sue LI, Bachalakuri J, Henry-Watson J, Sasse J, Boyer S, Shirohi S, Brooks R, Eschbacher J, White CL III, Akiyama H, Caviness J, Shill HA, Connor DJ, Sabbagh MN, Walker DG, Arizona Parkinson’s Disease Consortium (2009) Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol 117:613–634

    Article  PubMed  PubMed Central  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 (2010) Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 119:689–702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blesa J, Trigo-Damas I, Del Rey NL, Obeso JA (2018) The use of nonhuman primate models to understand processes in Parkinson’s disease. J Neural Transm (Vienna) 125:325–335

    Article  CAS  Google Scholar 

  • Bloch A, Probst A, Bissig H, Adams H, Tolnay M (2006) Alpha-synuclein pathology of the spinal and peripheral autonomic nervous system in neurologically unimpaired elderly subjects. Neuropathol Appl Neurobiol 32:284–295

    Article  CAS  PubMed  Google Scholar 

  • Braak H, Del Tredici K (2008) Nervous system pathology in sporadic Parkinson disease. Neurology 70:1916–1925

    Article  PubMed  Google Scholar 

  • Braak H, Del Tredici K (2016) Potential pathways of abnormal tau and alpha-synuclein dissemination in sporadic Alzheimer’s and Parkinson’s diseases. Cold Spring Harb Perspect Biol. https://doi.org/10.1101/cshperspect.a023630

    Article  PubMed  PubMed Central  Google Scholar 

  • Braak H, Del Tredici K (2017) Neuropathological staging of brain pathology in sporadic Parkinson’s disease: separating the wheat from the chaff. J Parkinsons Dis 7:S73–S87

    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 24:197–211

    Article  PubMed  Google Scholar 

  • Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318:121–134

    Article  PubMed  Google Scholar 

  • Braak H, Rub U, Jansen Steur EN, Del Tredici K, de Vos RA (2005) Cognitive status correlates with neuropathologic stage in Parkinson disease. Neurology 64:1404–1410

    Article  CAS  PubMed  Google Scholar 

  • Braak H, Bohl JR, Muller CM, Rub U, de Vos RA, Del Tredici K (2006) Stanley Fahn Lecture 2005: the staging procedure for the inclusion body pathology associated with sporadic Parkinson’s disease reconsidered. Mov Disord 21:2042–2051

    Article  PubMed  Google Scholar 

  • Brundin P, Melki R (2017) Prying into the prion hypothesis for Parkinson’s disease. J Neurosci 37:9808–9818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burke RE, Dauer WT, Vonsattel JP (2008) A critical evaluation of the Braak staging scheme for Parkinson’s disease. Ann Neurol 64:485–491

    Article  PubMed  PubMed Central  Google Scholar 

  • Chartier S, Duyckaerts C (2018) Is Lewy pathology in the human nervous system chiefly an indicator of neuronal protection or of toxicity? Cell Tissue Res. https://doi.org/10.1007/s00441-018-2854-6

    Article  PubMed  Google Scholar 

  • Collinge J, Clarke AR (2007) A general model of prion strains and their pathogenicity. Science 318:930–936

    Article  CAS  PubMed  Google Scholar 

  • DelleDonne A, Klos KJ, Fujishiro H, Ahmed Z, Parisi JE, Josephs KA, Frigerio R, Burnett M, Wszolek ZK, Uitti RJ, Ahlskog JE, Dickson DW (2008) Incidental Lewy body disease and preclinical Parkinson disease. Arch Neurol 65:1074–1080

    Article  PubMed  Google Scholar 

  • Dickson DW, Fujishiro H, DelleDonne A, Menke J, Ahmed Z, Klos KJ, Josephs KA, Frigerio R, Burnett M, Parisi JE, Ahlskog JE (2008) Evidence that incidental Lewy body disease is pre-symptomatic Parkinson’s disease. Acta Neuropathol 115:437–444

    Article  PubMed  Google Scholar 

  • Dickson DW, Braak H, Duda JE, Duyckaerts C, Gasser T, Halliday GM, Hardy J, Leverenz JB, Del Tredici K, Wszolek ZK, Litvan I (2009) Neuropathological assessment of Parkinson’s disease: refining the diagnostic criteria. Lancet Neurol 8:1150–1157

    Article  CAS  PubMed  Google Scholar 

  • Dickson DW, Uchikado H, Fujishiro H, Tsuboi Y (2010) Evidence in favor of Braak staging of Parkinson’s disease. Mov Disord 25(Suppl 1):S78–S82

    Article  PubMed  Google Scholar 

  • Dijkstra AA, Voorn P, Berendse HW, Groenewegen HJ, Rozemuller AJ, van de Berg WD (2014) Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson’s disease. Mov Disord 29:1244–1251

    Article  PubMed  Google Scholar 

  • Ding ZT, Wang Y, Jiang YP, Hashizume Y, Yoshida M, Mimuro M, Inagaki T, Iwase T (2006) Characteristics of alpha-synucleinopathy in centenarians. Acta Neuropathol 111:450–458

    Article  PubMed  Google Scholar 

  • Donadio V, Incensi A, Rizzo G, Capellari S, Pantieri R, Stanzani Maserati M, Devigili G, Eleopra R, Defazio G, Montini F, Baruzzi A, Liguori R (2017) A new potential biomarker for dementia with Lewy bodies: skin nerve alpha-synuclein deposits. Neurology 89:318–326

    Article  CAS  PubMed  Google Scholar 

  • Duffy MF, Collier TJ, Patterson JR, Kemp CJ, Luk KC, Tansey MG, Paumier KL, Kanaan NM, Fischer DL, Polinski NK, Barth OL, Howe JW, Vaikath NN, Majbour NK, El-Agnaf OMA, Sortwell CE (2018) Lewy body-like alpha-synuclein inclusions trigger reactive microgliosis prior to nigral degeneration. J Neuroinflammation 15:129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Erskine D, Patterson L, Alexandris A, Hanson PS, McKeith IG, Attems J, Morris CM (2018) Regional levels of physiological alpha-synuclein are directly associated with Lewy body pathology. Acta Neuropathol 135:153–154

    Article  CAS  PubMed  Google Scholar 

  • Fearnley JM, Lees AJ (1991) Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 114(Pt 5):2283–2301

    Article  PubMed  Google Scholar 

  • Ferman TJ, Boeve BF, Smith GE, Lin SC, Silber MH, Pedraza O, Wszolek Z, Graff-Radford NR, Uitti R, Van Gerpen J, Pao W, Knopman D, Pankratz VS, Kantarci K, Boot B, Parisi JE, Dugger BN, Fujishiro H, Petersen RC, Dickson DW (2011) Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies. Neurology 77:875–882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferrer I, Martinez A, Blanco R, Dalfo E, Carmona M (2011) Neuropathology of sporadic Parkinson disease before the appearance of parkinsonism: preclinical Parkinson disease. J Neural Transm (Vienna) 118:821–839

    Article  Google Scholar 

  • Frigerio R, Fujishiro H, Ahn TB, Josephs KA, Maraganore DM, Delledonne A, Parisi JE, Klos KJ, Boeve BF, Dickson DW, Ahlskog JE (2011) Incidental Lewy body disease: do some cases represent a preclinical stage of dementia with Lewy bodies? Neurobiol Aging 32:857–863

    Article  CAS  PubMed  Google Scholar 

  • Fumimura Y, Ikemura M, Saito Y, Sengoku R, Kanemaru K, Sawabe M, Arai T, Ito G, Iwatsubo T, Fukayama M, Mizusawa H, Murayama S (2007) Analysis of the adrenal gland is useful for evaluating pathology of the peripheral autonomic nervous system in Lewy body disease. J Neuropathol Exp Neurol 66:354–362

    Article  PubMed  Google Scholar 

  • Gaspar P, Gray F (1984) Dementia in idiopathic Parkinson’s disease. A neuropathological study of 32 cases. Acta Neuropathol 64:43–52

    Article  CAS  PubMed  Google Scholar 

  • Goedert M, Eisenberg DS, Crowther RA (2017a) Propagation of tau aggregates and neurodegeneration. Annu Rev Neurosci 40:189–210

    Article  CAS  PubMed  Google Scholar 

  • Goedert M, Masuda-Suzukake M, Falcon B (2017b) Like prions: the propagation of aggregated tau and alpha-synuclein in neurodegeneration. Brain 140:266–278

    Article  PubMed  Google Scholar 

  • Greffard S, Verny M, Bonnet AM, Beinis JY, Gallinari C, Meaume S, Piette F, Hauw JJ, Duyckaerts C (2006) Motor score of the Unified Parkinson Disease Rating Scale as a good predictor of Lewy body-associated neuronal loss in the substantia nigra. Arch Neurol 63:584–588

    Article  PubMed  Google Scholar 

  • Greffard S, Verny M, Bonnet AM, Seilhean D, Hauw JJ, Duyckaerts C (2010) 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 31:99–103

    Article  CAS  PubMed  Google Scholar 

  • Guo JL, Covell DJ, Daniels JP, Iba M, Stieber A, Zhang B, Riddle DM, Kwong LK, Xu Y, Trojanowski JQ, Lee VM (2013) Distinct alpha-synuclein strains differentially promote tau inclusions in neurons. Cell 154:103–117

    Article  CAS  PubMed  Google Scholar 

  • Halliday GM, McCann H (2010) The progression of pathology in Parkinson’s disease. Ann N Y Acad Sci 1184:188–195

    Article  PubMed  Google Scholar 

  • Halliday G, Murphy K (2010) Pathology of Parkinson’s disease—an overview. In: Schapira AHV, Lang AET, Fahn S (eds) Movement disorders 4. Saunders-Elsevier, Philadelphia, pp 132–154

    Chapter  Google Scholar 

  • Halliday GM, Stevens CH (2011) Glia: initiators and progressors of pathology in Parkinson’s disease. Mov Disord 26:6–17

    Article  PubMed  Google Scholar 

  • Halliday GM, Del Tredici K, Braak H (2006) Critical appraisal of brain pathology staging related to presymptomatic and symptomatic cases of sporadic Parkinson’s disease. J Neural Transm Suppl:99–103

    Google Scholar 

  • Halliday G, Hely M, Reid W, Morris J (2008) The progression of pathology in longitudinally followed patients with Parkinson’s disease. Acta Neuropathol 115:409–415

    Article  PubMed  Google Scholar 

  • Halliday GM, Song YJ, Harding AJ (2011) Striatal beta-amyloid in dementia with Lewy bodies but not Parkinson’s disease. J Neural Transm 118:713–719

    Article  CAS  PubMed  Google Scholar 

  • Iacono D, Geraci-Erck M, Rabin ML, Adler CH, Serrano G, Beach TG, Kurlan R (2015) Parkinson disease and incidental Lewy body disease: just a question of time? Neurology 85:1670–1679

    Article  PubMed  PubMed Central  Google Scholar 

  • Jellinger KA (2003) Alpha-synuclein pathology in Parkinson and Alzheimer disease brain: incidence and topographic distribution—a pilot study. Acta Neuropathol 106:191–201

    Article  PubMed  Google Scholar 

  • Jellinger KA (2004) Lewy body-related alpha-synucleinopathy in the aged human brain. J Neural Transm (Vienna) 111:1219–1235

    Article  CAS  Google Scholar 

  • Jellinger KA (2009a) A critical evaluation of current staging of alpha-synuclein pathology in Lewy body disorders. Biochim Biophys Acta 1792:730–740

    Article  CAS  PubMed  Google Scholar 

  • Jellinger KA (2009b) Formation and development of Lewy pathology: a critical update. J Neurol 256(Suppl 3):270–279

    Article  PubMed  Google Scholar 

  • Jellinger KA (2012) Neuropathology of sporadic Parkinson’s disease: evaluation and changes of concepts. Mov Disord 27:8–30

    Article  CAS  PubMed  Google Scholar 

  • Jellinger KA (2014) Neuropathology of Parkinson’s disease. In: Thomas M (ed) Inflammation in Parkinson’s disease: scientific and clinical aspects. Springer, New York, pp 25–47

    Google Scholar 

  • Kalaitzakis ME, Graeber MB, Gentleman SM, Pearce RK (2008) The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson’s disease: a critical analysis of alpha-synuclein staging. Neuropathol Appl Neurobiol 34:284–295

    Article  CAS  PubMed  Google Scholar 

  • Kempster PA, O’Sullivan SS, Holton JL, Revesz T, Lees AJ (2010) Relationships between age and late progression of Parkinson’s disease: a clinico-pathological study. Brain 133:1755–1762

    Article  PubMed  Google Scholar 

  • Kingsbury AE, Bandopadhyay R, Silveira-Moriyama L, Ayling H, Kallis C, Sterlacci W, Maeir H, Poewe W, Lees AJ (2010) Brain stem pathology in Parkinson’s disease: an evaluation of the Braak staging model. Mov Disord 25:2508–2515

    Article  PubMed  Google Scholar 

  • Klingelhoefer L, Reichmann H (2015) Pathogenesis of Parkinson disease—the gut–brain axis and environmental factors. Nat Rev Neurol 11:625–636

    Article  CAS  PubMed  Google Scholar 

  • Kordower JH, Olanow CW, Dodiya HB, Chu Y, Beach TG, Adler CH, Halliday GM, Bartus RT (2013) Disease duration and the integrity of the nigrostriatal system in Parkinson’s disease. Brain 136:2419–2431

    Article  PubMed  PubMed Central  Google Scholar 

  • Kosaka K, Tsuchiya K, Yoshimura M (1988) Lewy body disease with and without dementia: a clinicopathological study of 35 cases. Clin Neuropathol 7:299–305

    CAS  PubMed  Google Scholar 

  • Kovacs GG, Milenkovic IJ, Preusser M, Budka H (2008) Nigral burden of alpha-synuclein correlates with striatal dopamine deficit. Mov Disord 23:1608–1612

    Article  PubMed  Google Scholar 

  • Kovacs GG, Wagner U, Dumont B, Pikkarainen M, Osman AA, Streichenberger N, Leisser I, Verchere J, Baron T, Alafuzoff I, Budka H, Perret-Liaudet A, Lachmann I (2012) An antibody with high reactivity for disease-associated alpha-synuclein reveals extensive brain pathology. Acta Neuropathol 124:37–50

    Article  CAS  PubMed  Google Scholar 

  • Lebouvier T, Pouclet H, Coron E, Drouard A, N’Guyen JM, Roy M, Vavasseur F, Bruley des Varannes S, Damier P, Neunlist M, Derkinderen P, Rouaud T (2011) Colonic neuropathology is independent of olfactory dysfunction in Parkinson’s disease. J Parkinsons Dis 1:389–394

    PubMed  Google Scholar 

  • Leverenz JB, Hamilton R, Tsuang DW, Schantz A, Vavrek D, Larson EB, Kukull WA, Lopez O, Galasko D, Masliah E, Kaye J, Woltjer R, Clark C, Trojanowski JQ, Montine TJ (2008) Empiric refinement of the pathologic assessment of Lewy-related pathology in the dementia patient. Brain Pathol 18:220–224

    Article  PubMed  PubMed Central  Google Scholar 

  • Lewis SJ, Foltynie T, Blackwell AD, Robbins TW, Owen AM, Barker RA (2005) Heterogeneity of Parkinson’s disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 76:343–348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Longhena F, Faustini G, Missale C, Pizzi M, Spano P, Bellucci A (2017) The contribution of alpha-synuclein spreading to Parkinson’s disease synaptopathy. Neural Plast 2017:5012129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Longhena F, Faustini G, Missale C, Pizzi M, Bellucci A (2018) Dopamine transporter/alpha-synuclein complexes are altered in the post mortem caudate putamen of Parkinson’s disease: an in situ proximity ligation assay study. Int J Mol Sci 19:E1611

    Article  CAS  PubMed  Google Scholar 

  • McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, Lennox G, Quinn NP, Edwardson JA, Ince PG, Bergeron C, Burns A, Miller BL, Lovestone S, Collerton D, Jansen EN, Ballard C, de Vos RA, Wilcock GK, Jellinger KA, Perry RH (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 47:1113–1124

    Article  CAS  PubMed  Google Scholar 

  • McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, Aarsland D, Galvin J, Attems J, Ballard CG, Bayston A, Beach TG, Blanc F, Bohnen N, Bonanni L, Bras J, Brundin P, Burn D, Chen-Plotkin A, Duda JE, El-Agnaf O, Feldman H, Ferman TJ, Ffytche D, Fujishiro H, Galasko D, Goldman JG, Gomperts SN, Graff-Radford NR, Honig LS, Iranzo A, Kantarci K, Kaufer D, Kukull W, Lee VMY, Leverenz JB, Lewis S, Lippa C, Lunde A, Masellis M, Masliah E, McLean P, Mollenhauer B, Montine TJ, Moreno E, Mori E, Murray M, O’Brien JT, Orimo S, Postuma RB, Ramaswamy S, Ross OA, Salmon DP, Singleton A, Taylor A, Thomas A, Tiraboschi P, Toledo JB, Trojanowski JQ, Tsuang D, Walker Z, Yamada M, Kosaka K (2017) Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology 89:88–100

    Article  PubMed  PubMed Central  Google Scholar 

  • Mikolaenko I, Pletnikova O, Kawas CH, O’Brien R, Resnick SM, Crain B, Troncoso JC (2005) Alpha-synuclein lesions in normal aging, Parkinson disease, and Alzheimer disease: evidence from the Baltimore Longitudinal Study of Aging (BLSA). J Neuropathol Exp Neurol 64:156–162

    Article  CAS  PubMed  Google Scholar 

  • Milber JM, Noorigian JV, Morley JF, Petrovitch H, White L, Ross GW, Duda JE (2012) Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease. Neurology 79:2307–2314

    Article  PubMed  PubMed Central  Google Scholar 

  • Mori F, Nishie M, Kakita A, Yoshimoto M, Takahashi H, Wakabayashi K (2006) Relationship among alpha-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra. J Neuropathol Exp Neurol 65:808–815

    Article  CAS  PubMed  Google Scholar 

  • Müller CM, de Vos RA, Maurage CA, Thal DR, Tolnay M, Braak H (2005) Staging of sporadic Parkinson disease-related alpha-synuclein pathology: inter- and intra-rater reliability. J Neuropathol Exp Neurol 64:623–628

    Article  PubMed  Google Scholar 

  • O'Keeffe GW, Sullivan AM (2018) Evidence for dopaminergic axonal degeneration as an early pathological process in Parkinson's disease. Parkinsonism Relat Disord. https://doi.org/10.1016/j.parkreldis.2018.06.025

    Article  PubMed  Google Scholar 

  • Orimo S, Takahashi A, Uchihara T, Mori F, Kakita A, Wakabayashi K, Takahashi H (2007) Degeneration of cardiac sympathetic nerve begins in the early disease process of Parkinson’s disease. Brain Pathol 17:24–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parkkinen L, Soininen H, Alafuzoff I (2003) Regional distribution of alpha-synuclein pathology in unimpaired aging and Alzheimer disease. J Neuropathol Exp Neurol 62:363–367

    Article  CAS  PubMed  Google Scholar 

  • Parkkinen L, Pirttila T, Alafuzoff I (2008) Applicability of current staging/categorization of alpha-synuclein pathology and their clinical relevance. Acta Neuropathol 115:399–407

    Article  PubMed  PubMed Central  Google Scholar 

  • Parkkinen L, O’Sullivan SS, Collins C, Petrie A, Holton JL, Revesz T, Lees AJ (2011) Disentangling the relationship between lewy bodies and nigral neuronal loss in Parkinson’s disease. J Parkinsons Dis 1:277–286

    CAS  PubMed  PubMed Central  Google Scholar 

  • Peelaerts W, Bousset L, Van der Perren A, Moskalyuk A, Pulizzi R, Giugliano M, Van den Haute C, Melki R, Baekelandt V (2015) Alpha-synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature 522:340–344

    Article  CAS  PubMed  Google Scholar 

  • Peelaerts W, Bousset L, Baekelandt V, Melki R (2018) a-Synuclein strains and seeding in Parkinson’s disease, incidental Lewy body disease, dementia with Lewy bodies and multiple system atrophy: similarities and differences. Cell Tissue Res. https://doi.org/10.1007/s00441-00018-02839-00445 (online)

    Article  PubMed  Google Scholar 

  • Peng C, Gathagan RJ, Covell DJ, Medellin C, Stieber A, Robinson JL, Zhang B, Pitkin RM, Olufemi MF, Luk KC, Trojanowski JQ, Lee VM (2018) Cellular milieu imparts distinct pathological alpha-synuclein strains in alpha-synucleinopathies. Nature. https://doi.org/10.1038/s41586-41018-40104-41584 (online)

    Article  PubMed  PubMed Central  Google Scholar 

  • Rajput AH, Rajput EF (2017) Octogenarian parkinsonism—clinicopathological observations. Parkinsonism Relat Disord 37:50–57

    Article  PubMed  Google Scholar 

  • Rey NL, George S, Brundin P (2016) Review: spreading the word: precise animal models and validated methods are vital when evaluating prion-like behaviour of alpha-synuclein. Neuropathol Appl Neurobiol 42:51–76

    Article  CAS  PubMed  Google Scholar 

  • Rietdijk CD, Perez-Pardo P, Garssen J, van Wezel RJ, Kraneveld AD (2017) Exploring Braak’s hypothesis of Parkinson’s disease. Front Neurol 8:37

    Article  PubMed  PubMed Central  Google Scholar 

  • Schneider SA, Alcalay RN (2017) Neuropathology of genetic synucleinopathies with parkinsonism: review of the literature. Mov Disord 32:1504–1523

    Article  PubMed  PubMed Central  Google Scholar 

  • Selikhova M, Williams DR, Kempster PA, Holton JL, Revesz T, Lees AJ (2009) A clinico-pathological study of subtypes in Parkinson’s disease. Brain 132:2947–2957

    Article  CAS  PubMed  Google Scholar 

  • Steiner JA, Quansah E, Brundin P (2018) The concept of alpha-synuclein as a prion-like protein: ten years after. Cell Tissue Res. https://doi.org/10.1007/s00441-018-2814-1

    Article  PubMed  PubMed Central  Google Scholar 

  • Surmeier DJ, Obeso JA, Halliday GM (2017) Selective neuronal vulnerability in Parkinson disease. Nat Rev Neurosci 18:101–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toledo JB, Gopal P, Raible K, Irwin DJ, Brettschneider J, Sedor S, Waits K, Boluda S, Grossman M, Van Deerlin VM, Lee EB, Arnold SE, Duda JE, Hurtig H, Lee VM, Adler CH, Beach TG, Trojanowski JQ (2016) Pathological alpha-synuclein distribution in subjects with coincident Alzheimer’s and Lewy body pathology. Acta Neuropathol 131:393–409

    Article  CAS  PubMed  Google Scholar 

  • Tolosa E, Santamaria J, Gaig C, Compta Y (2010) Nonmotor aspects of Parkinson’s disease. In: Schapira AHV, Lang AET, Fahn S (eds) Movement disorders 4. Saunders-Elsevier, Philadelphia, pp 229–251

    Chapter  Google Scholar 

  • Uchihara T (2017) An order in Lewy body disorders: retrograde degeneration in hyperbranching axons as a fundamental structural template accounting for focal/multifocal Lewy body disease. Neuropathology 37:129–149

    Article  CAS  PubMed  Google Scholar 

  • Vale TC, Barbosa MT, Resende EPF, Maia DP, Cunningham MCQ, Guimaraes HC, Machado JCB, Teixeira AL, Cardoso F, Caramelli P (2018) Parkinsonism in a population-based study of individuals aged 75+ years: The Pieta study. Parkinsonism Relat Disord. https://doi.org/10.1016/j.parkreldis.2018.06.030

    Article  PubMed  Google Scholar 

  • van de Berg WD, Hepp DH, Dijkstra AA, Rozemuller JA, Berendse HW, Foncke E (2012) Patterns of alpha-synuclein pathology in incidental cases and clinical subtypes of Parkinson’s disease. Parkinsonism Relat Disord 18(Suppl 1):S28–S30

    Article  PubMed  Google Scholar 

  • Visanji NP, Brooks PL, Hazrati LN, Lang AE (2013) The prion hypothesis in Parkinson’s disease: Braak to the future. Acta Neuropathol Commun 1:2

    Article  PubMed  PubMed Central  Google Scholar 

  • Wakabayashi K, Takahashi H, Oyanagi K, Ikuta F (1993) Incidental occurrence of Lewy bodies in the brains of elderly patients—the relevance to aging and Parkinson’s disease. No To Shinkei 45:1033–1038

    CAS  PubMed  Google Scholar 

  • Wakisaka Y, Furuta A, Tanizaki Y, Kiyohara Y, Iida M, Iwaki T (2003) Age-associated prevalence and risk factors of Lewy body pathology in a general population: the Hisayama study. Acta Neuropathol 106:374–382

    Article  PubMed  Google Scholar 

  • Walker LC, Jucker M (2015) Neurodegenerative diseases: expanding the prion concept. Annu Rev Neurosci 38:87–103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weisman D, Cho M, Taylor C, Adame A, Thal LJ, Hansen LA (2007) In dementia with Lewy bodies, Braak stage determines phenotype, not Lewy body distribution. Neurology 69:356–359

    Article  CAS  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 70:1042–1048

    Article  CAS  PubMed  Google Scholar 

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  1. Institute of Clinical Neurobiology, Alberichgasse 5/13, 1150, Vienna, Austria

    Kurt A. Jellinger

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  1. Kurt A. Jellinger
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Correspondence to Kurt A. Jellinger.

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Dedicated to Professor Arvid Carlsson, founding Editor of the Journal of Neural Transmission, awarded the Noble Prize in Physiology or Medicine 2000, who will celebrate his 96th birthday on January 25, 2019.

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Jellinger, K.A. Is Braak staging valid for all types of Parkinson’s disease?. J Neural Transm 126, 423–431 (2019). https://doi.org/10.1007/s00702-018-1898-9

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  • DOI: https://doi.org/10.1007/s00702-018-1898-9

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