Cited by 395Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeuroinflammation and Neurodegeneration Mechanisms

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Exploring Braak’s Hypothesis of Parkinson’s Disease

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Rietdijk, Carmen D., Perez-Pardo, Paula, Garssen, Johan, van Wezel, Richard J. A., Kraneveld, Aletta D.·2017·Frontiers in Neurology

DOI 10.3389/fneur.2017.00037PMC PMC5304413

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Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder for which there is no cure. Most patients suffer from sporadic PD, which is likely caused by a combination of genetic and environmental factors. Braak’s hypothesis states that sporadic PD is caused by a pathogen that enters the body via the nasal cavity, and subsequently is swallowed and reaches the gut, initiating Lewy pathology (LP) in the nose and the digestive tract. A staging system describing the spread of LP from the peripheral to the central nervous system was also postulated by the same research group. There has been criticism to the Braak’s hypothesis, in part because not all patients follow the proposed staging system. Here, we review literature that either supports or criticizes the Braak’s hypothesis, focused on the enteric route, digestive problems in patients, the spread of LP on a tissue and a cellular level, and the toxicity of the protein αSynuclein (αSyn), which is the major constituent of LP. We conclude that the Braak’s hypothesis is supported by in vitro, in vivo and clinical evidence. However, we also conclude that the staging system of Braak only describes a specific subset of patients with young onset and long duration of the disease.

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Figure 1 A schematic representation of the Braak’s hypothesis of Parkinson’s disease (PD). Microbial products come into contact with olfactory and/or enteric neurons, which trigger the aggregation of α-Synuclein (1 and 2). The aggregated α-Synuclein spreads toward the central nervous system via the olfactory bulb and the vagus nerve (3 and 4). Eventually, the aggregated α-Synuclein arrives at the substantia nigra (5). Genetic factors are likely to contribute to PD, but the exact mechanism remains to be elucidated (6).CC BY · PubMed Central

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Staging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., et al. (1997) · Science · doi:10.1126/science.276.5321.2045 · Cited by 8,240
Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa
De Filippo, C., Cavalieri, D., Di Paola, M., Ramazzotti, M., Poullet, J. B., Massart, S., Collini, S., Pieraccini, G., & Lionetti, P. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005963107 · Cited by 5,579
Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis
Langston, J. W., Ballard, P., Tetrud, J. W., & Irwin, I. (1983) · Science · doi:10.1126/science.6823561 · Cited by 4,914
α-Synuclein Locus Triplication Causes Parkinson's Disease
Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R., et al. (2003) · Science · doi:10.1126/science.1090278 · Cited by 4,383
AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's disease
Krüger, R., Kuhn, W., Müller, T., Woitalla, D., Graeber, M., Kösel, S., Przuntek, H., Epplen, J. T., Schols, L., & Riess, O. (1998) · Nature Genetics · doi:10.1038/ng0298-106 · Cited by 3,836
The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice
Turnbaugh, P. J., Ridaura, V. K., Faith, J. J., Rey, F. E., Knight, R., & Gordon, J. I. (2009) · Science Translational Medicine · doi:10.1126/scitranslmed.3000322 · Cited by 3,058 · cited 1×
“Dietary components and dietary patterns have a considerable effect on the composition of the gut microbiome (66).”
Background
The new mutation, E46K, of α‐synuclein causes parkinson and Lewy body dementia
Zarranz, J. J., Alegre, J., Gómez‐Esteban, J. C., Lezcano, E., Ros, R., Ampuero, I., Vidal, L., Hoenicka, J., Rodriguez, O., Atarés, B., et al. (2004) · Annals of Neurology · doi:10.1002/ana.10795 · Cited by 2,737
Pathological α-Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice
Luk, K. C., Kehm, V., Carroll, J., Zhang, B., O’Brien, P., Trojanowski, J. Q., & Lee, V. M.-Y. (2012) · Science · doi:10.1126/science.1227157 · Cited by 2,563
Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis
Singh, N., Gurav, A., Sivaprakasam, S., Brady, E., Padia, R., Shi, H., Thangaraju, M., Prasad, P. D., Manicassamy, S., Munn, D. H., et al. (2014) · Immunity · doi:10.1016/j.immuni.2013.12.007 · Cited by 2,368
The Sydney multicenter study of Parkinson's disease: The inevitability of dementia at 20 years
Hely, M. A., Reid, W. G. J., ADENA, M. A., Halliday, G. M., & Morris, J. G. (2008) · Movement Disorders · doi:10.1002/mds.21956 · Cited by 2,346
α-synuclein locus duplication as a cause of familial Parkinson's disease
Chartier-Harlin, M.-C., Kachergus, J., Roumier, C., Mouroux, V., Douay, X., Lincoln, S., Levecque, C., Larvor, L., Andrieux, J., Hulihan, M., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17103-1 · Cited by 2,029
Gut microbiota are related to Parkinson's disease and clinical phenotype
Scheperjans, F., Aho, V., Pereira, P. A. B., Koskinen, K., Paulin, L., Pekkonen, E., Haapaniemi, E., Kaakkola, S., Eerola‐Rautio, J., Pohja, M., et al. (2015) · Movement Disorders · doi:10.1002/mds.26069 · Cited by 1,968
Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation
Li, J.-Y., Englund, E., Holton, J. L., Soulet, D., Hagell, P., Lees, A. J., Lashley, T., Quinn, N. P., Rehncrona, S., Björklund, A., et al. (2008) · Nature Medicine · doi:10.1038/nm1746 · Cited by 1,845
Incidence of Parkinson's Disease: Variation by Age, Gender, and Race/Ethnicity
Eeden, S. K. V. D. (2003) · American Journal of Epidemiology · doi:10.1093/aje/kwg068 · Cited by 1,805
Lewy body–like pathology in long-term embryonic nigral transplants in Parkinson's disease
Kordower, J. H., Chu, Y., Hauser, R. A., Freeman, T. B., & Olanow, C. W. (2008) · Nature Medicine · doi:10.1038/nm1747 · Cited by 1,722
Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen
Braak, H., R�b, U., Gai, W. P., & Del Tredici, K. (2003) · Journal of Neural Transmission · doi:10.1007/s00702-002-0808-2 · Cited by 1,683
Self-propagation of pathogenic protein aggregates in neurodegenerative diseases
Jucker, M., & Walker, L. C. (2013) · Nature · doi:10.1038/nature12481 · Cited by 1,663
Exogenous α-Synuclein Fibrils Induce Lewy Body Pathology Leading to Synaptic Dysfunction and Neuron Death
Volpicelli-Daley, L. A., Luk, K. C., Patel, T. P., Tanik, S. A., Riddle, D. M., Stieber, A., Meaney, D. F., Trojanowski, J. Q., & Lee, V. M.-Y. (2011) · Neuron · doi:10.1016/j.neuron.2011.08.033 · Cited by 1,569
Rotenone, Paraquat, and Parkinson’s Disease
Tanner, C. M., Kamel, F., Ross, G. W., Hoppin, J. A., Goldman, S. M., Korell, M., Marras, C., Bhudhikanok, G. S., Kasten, M., Chade, A. R., et al. (2011) · Environmental Health Perspectives · doi:10.1289/ehp.1002839 · Cited by 1,565
Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein
Desplats, P., Lee, H.-J., Bae, E.-J., Patrick, C., Rockenstein, E., Crews, L., Spencer, B., Masliah, E., & Lee, S.-J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903691106 · Cited by 1,485
Gastric α-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology
Braak, H., de Vos, R. A. I., Bohl, J., & Del Tredici, K. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2005.11.012 · Cited by 1,354
Intracerebral inoculation of pathological α-synuclein initiates a rapidly progressive neurodegenerative α-synucleinopathy in mice
Luk, K. C., Kehm, V. M., Zhang, B., O’Brien, P., Trojanowski, J. Q., & Lee, V. M. ‐. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20112457 · Cited by 1,136
Cell-produced α-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival
Emmanouilidou, E., Melachroinou, K., Roumeliotis, T., Garbis, S. D., Ntzouni, M., Margaritis, L. H., Stefanis, L., & Vekrellis, K. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5699-09.2010 · Cited by 1,115 · cited 2×
“In a different study, the uptake was only found in proliferating SH-SY5Y neurons, but not in differentiated SH-SY5Y neurons, which could be due to the type of αSyn that was different from the other studies (radioactively labeled cell produced αSyn, versus different forms of recombinant human or non-human αSyn) (96).”
BackgroundResult
Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway
Lehnardt, S., Massillon, L., Follett, P., Jensen, F. E., Ratan, R., Rosenberg, P. A., Volpe, J. J., & Vartanian, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1432609100 · Cited by 1,052
Parkinson's disease: a dual‐hit hypothesis
Hawkes, C. H., Del Tredici, K., & Braak, H. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00874.x · Cited by 1,021
Gastrointestinal Dysfunction in Parkinson’s Disease
Fasano, A., Visanji, N. P., Liu, L. W. C., Lang, A. E., & Pfeiffer, R. F. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00007-1 · Cited by 1,016
Increased Intestinal Permeability Correlates with Sigmoid Mucosa alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson's Disease
Forsyth, C. B., Shannon, K. M., Kordower, J. H., Voigt, R. M., Shaikh, M., Jaglin, J. A., Estes, J. D., Dodiya, H. B., & Keshavarzian, A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028032 · Cited by 974
Exogenous α-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells
Luk, K. C., Song, C., O'Brien, P., Stieber, A., Branch, J. R., Brunden, K. R., Trojanowski, J. Q., & Lee, V. M.-Y. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908005106 · Cited by 938
Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats
Holmqvist, S., Chutna, O., Bousset, L., Aldrin-Kirk, P., Li, W., Björklund, T., Wang, Z.-Y., Roybon, L., Melki, R., & Li, J.-Y. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1343-6 · Cited by 925
Multi-organ distribution of phosphorylated α-synuclein histopathology in subjects with Lewy body disorders
Arizona Parkinson’s Disease Consortium, Beach, T. G., Adler, C. H., Sue, L. I., Vedders, L., Lue, L., White III, C. L., Akiyama, H., Caviness, J. N., Shill, H. A., et al. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0664-3 · Cited by 911
Exosomal cell-to-cell transmission of alpha synuclein oligomers
Danzer, K. M., Kranich, L. R., Ruf, W. P., Cagsal‐Getkin, O., Winslow, A. R., Zhu, L., Vanderburg, C. R., & McLean, P. J. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-42 · Cited by 879
Direct Transfer of α-Synuclein from Neuron to Astroglia Causes Inflammatory Responses in Synucleinopathies
Lee, H.-J., Suk, J.-E., Patrick, C., Bae, E.-J., Cho, J.-H., Rho, S., Hwang, D., Masliah, E., & Lee, S.-J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.081125 · Cited by 877
α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells
Hansen, C., Angot, E., Bergström, A.-L., Steiner, J. A., Pieri, L., Paul, G., Outeiro, T. F., Melki, R., Kallunki, P., Fog, K., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci43366 · Cited by 842
Intravesicular Localization and Exocytosis of α-Synuclein and its Aggregates
Lee, H.-J., Patel, S. S., & Lee, S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0692-05.2005 · Cited by 826
Vagotomy and subsequent risk of Parkinson's disease
Svensson, E., Horváth‐Puhó, E., Thomsen, R. W., Djurhuus, J. C., Pedersen, L., Borghammer, P., & Sørensen, H. T. (2015) · Annals of Neurology · doi:10.1002/ana.24448 · Cited by 806
Where Does Parkinson Disease Pathology Begin in the Brain?
Del Tredici, K., Rüb, U., de Vos, R. A. I., Bohl, J. R. E., & Braak, H. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.5.413 · Cited by 773
G51D α‐synuclein mutation causes a novel Parkinsonian–pyramidal syndrome
Lesage, S., Anheim, M., Letournel, F., Bousset, L., Honoré, A., Rozas, N., Pieri, L., Madiona, K., Dürr, A., Melki, R., et al. (2013) · Annals of Neurology · doi:10.1002/ana.23894 · Cited by 741
Association of olfactory dysfunction with risk for future Parkinson's disease
Ross, G. W., Petrovitch, H., Abbott, R. D., Tanner, C. M., Popper, J. S., Masaki, K., Launer, L. J., & White, L. R. (2007) · Annals of Neurology · doi:10.1002/ana.21291 · Cited by 739
Comparison of kindreds with parkinsonism and α‐synuclein genomic multiplications
Farrer, M. J., Kachergus, J. M., Forno, L. S., Lincoln, S., Wang, D., Hulihan, M., Maraganore, D. M., Gwinn, K. A., Wszołek, Z. K., Dickson, D. W., et al. (2004) · Annals of Neurology · doi:10.1002/ana.10846 · Cited by 711
Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction
the Arizona Parkinson’s Disease Consortium, Beach, T. G., Adler, C. H., Lue, L., Sue, L. I., Bachalakuri, J., Henry-Watson, J., Sasse, J., Boyer, S., Shirohi, S., et al. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0538-8 · Cited by 698
Toll‐like receptor 4 is required for α‐synuclein dependent activation of microglia and astroglia
Fellner, L., Irschick, R., Schanda, K., Reindl, M., Klimaschewski, L., Poewe, W., Wenning, G. K., & Stefanova, N. (2013) · Glia · doi:10.1002/glia.22437 · Cited by 697
Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3
Mao, X., Ou, M. T., Karuppagounder, S. S., Kam, T.-I., Yin, X., Xiong, Y., Ge, P., Umanah, G. E., Brahmachari, S., Shin, J.-H., et al. (2016) · Science · doi:10.1126/science.aah3374 · Cited by 690
Alpha‐synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease
Appel‐Cresswell, S., Vilariño‐Güell, C., Encarnacion, M. J., Sherman, H. E., Yu, I. S., Shah, B., Weir, D., Thompson, C., Szu‐Tu, C., Trinh, J., et al. (2013) · Movement Disorders · doi:10.1002/mds.25421 · Cited by 687
Lewy body extracts from Parkinson disease brains trigger α‐synuclein pathology and neurodegeneration in mice and monkeys
Recasens, A., Dehay, B., Bové, J., Carballo‐Carbajal, I., Doveró, S., Pérez‐Villalba, A., Fernagut, P., Blesa, J., Parent, A., Perier, C., et al. (2013) · Annals of Neurology · doi:10.1002/ana.24066 · Cited by 670
Neuroinflammation in Parkinson's disease
Hirsch, E. C., Vyas, S., & Hunot, S. (2012) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(11)70065-7 · Cited by 657
Colonic inflammation in Parkinson's disease
Devos, D., Lebouvier, T., Lardeux, B., Biraud, M., Rouaud, T., Pouclet, H., Coron, E., Bruley des Varannes, S., Naveilhan, P., Nguyen, J.-M., et al. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.09.007 · Cited by 627
Prevalence and incidence of Parkinson's disease in Europe
von Campenhausen, S., Bornschein, B., Wick, R., Bötzel, K., Sampaio, C., Poewe, W. H., Oertel, W. H., Siebert, U., Berger, K., & Dodel, R. C. (2005) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2005.04.007 · Cited by 624
Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations
Dehay, B., Bourdenx, M., Gorry, P., Przedborski, S., Vila, M., Hunot, S., Singleton, A., Olanow, C. W., Merchant, K., Bézard, E., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00006-x · Cited by 556
Parkinson's disease: the presence of Lewy bodies in Auerbach's and Meissner's plexuses
Wakabayashi, K., Takahashi, H., Takeda, S., Ohama, E., & Ikuta, F. (1988) · Acta Neuropathologica · doi:10.1007/bf00687767 · Cited by 528
Progression of Parkinson's disease pathology is reproduced by intragastric administration of rotenone in mice
Pan-Montojo, F., Anichtchik, O., Dening, Y., Knels, L., Pursche, S., Jung, R., Jackson, S., Gille, G., Spillantini, M. G., Reichmann, H., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008762 · Cited by 524
Factors predictive of the development of Levodopa‐induced dyskinesia and wearing‐off in Parkinson's disease
Olanow, C. W., Kieburtz, K. D., Rascol, O., Poewe, W. H., Schapira, A. H. V., Emre, M., Nissinen, H., Leinonen, M., Stocchi, F., & Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE‐PD) Investigators (2013) · Movement Disorders · doi:10.1002/mds.25364 · Cited by 483
Early and Progressive Sensorimotor Anomalies in Mice Overexpressing Wild-Type Human α-Synuclein
Fleming, S. M., Salcedo, J. D., Fernagut, P., Rockenstein, E. M., Masliah, E., Levine, M. S., & Chesselet, M. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3080-04.2004 · Cited by 477
Assembly-dependent endocytosis and clearance of extracellular a-synuclein
Lee, H.-J., Suk, J.-E., Bae, E.-J., Lee, J.-H., Paik, S. R., & Lee, S.-J. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.01.017 · Cited by 470
Alpha-synuclein in colonic submucosa in early untreated Parkinson’s disease
Shannon, K. M., Keshavarzian, A., Mutlu, E., Dodiya, H. B., Daian, D., Jaglin, J. A., & Kordower, J. H. (2012) · Movement Disorders · doi:10.1002/mds.23838 · Cited by 469
A novel α-synuclein missense mutation in Parkinson disease
Proukakis, C., Dudzik, C. G., Brier, T., Mackay, D. S., Cooper, J. A. D., Millhauser, G. L., Houlden, H., & Schapira, A. H. V. (2013) · Neurology · doi:10.1212/wnl.0b013e31828727ba · Cited by 465
Olfaction in Parkinson's disease and related disorders
Doty, R. L. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.10.026 · Cited by 461
The type and quantity of dietary fat and carbohydrate alter faecal microbiome and short-chain fatty acid excretion in a metabolic syndrome ‘at-risk’ population
Fava, F., Gitau, R., Griffin, B. A., Gibson, G. R., Tuohy, K. M., & Lovegrove, J. A. (2012) · International Journal of Obesity · doi:10.1038/ijo.2012.33 · Cited by 440
Geographic and Ethnic Variation in Parkinson Disease: A Population-Based Study of US Medicare Beneficiaries
Willis, A. W., Evanoff, B., Lian, M., Criswell, S. R., & Racette, B. A. (2010) · Neuroepidemiology · doi:10.1159/000275491 · Cited by 436
Aggresomes Formed by α-Synuclein and Synphilin-1 Are Cytoprotective
Tanaka, M., Kim, Y. M., Lee, G., Junn, E., Iwatsubo, T., & Mouradian, M. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310994200 · Cited by 434
JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease
Hunot, S., Vila, M., Teismann, P., Davis, R. J., Hirsch, É. C., Przedborski, S., RAKIC, P. T., & Flavell, R. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307453101 · Cited by 430
Colonic biopsies to assess the neuropathology of Parkinson's disease and its relationship with symptoms
Lebouvier, T., Neunlist, M., Bruley des Varannes, S., Coron, E., Drouard, A., N'Guyen, J.-M., Chaumette, T., Tasselli, M., Paillusson, S., Flamand, M., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012728 · Cited by 427
Review: Sporadic Parkinson's disease: development and distribution ofα‐synuclein pathology
Tredici, K. D., & Braak, H. (2015) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12298 · Cited by 416
The progression of pathology in longitudinally followed patients with Parkinson’s disease
Halliday, G. M., Hely, M. A., Reid, W. G. J., & Morris, J. G. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0344-8 · Cited by 410
Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice
Pan-Montojo, F., Schwarz, M., Winkler, C., Arnhold, M., O'Sullivan, G. A., Pal, A., Said, J., Marsico, G., Verbavatz, J.-M., Rodrigo-Angulo, M., et al. (2012) · Scientific Reports · doi:10.1038/srep00898 · Cited by 405
Prion-like acceleration of a synucleinopathy in a transgenic mouse model
Mougenot, A.-L. J., Nicot, S., Bencsik, A. A., Morignat, E., Verchère, J., Lakhdar, L., Legastelois, S., & Baron, T. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.06.022 · Cited by 399
Neuron‐to‐neuron transmission of α‐synuclein fibrils through axonal transport
Freundt, E. C., Maynard, N., Clancy, E. K., Roy, S., Bousset, L., Sourigues, Y., Covert, M. W., Melki, R., Kirkegaard, K., & Brahic, M. (2012) · Annals of Neurology · doi:10.1002/ana.23747 · Cited by 394
Applicability of current staging/categorization of α-synuclein pathology and their clinical relevance
Parkkinen, L., Pirttilä, T., & Alafuzoff, I. I. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0346-6 · Cited by 377
Evidence that incidental Lewy body disease is pre-symptomatic Parkinson’s disease
Dickson, D. W., Fujishiro, H., DelleDonne, A., Menke, J., Ahmed, Z., Klos, K. J., Josephs, K. A., Frigerio, R., Burnett, M., Parisi, J. E., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0345-7 · Cited by 364
Motor Score of the Unified Parkinson Disease Rating Scale as a Good Predictor of Lewy Body–Associated Neuronal Loss in the Substantia Nigra
Greffard, S., Verny, M., Bonnet, A.-M., Beinis, J., Gallinari, C., Meaume, S., Piette, F., Hauw, J., & Duyckaerts, C. J. (2006) · Archives of Neurology · doi:10.1001/archneur.63.4.584 · Cited by 355
The Role of Inflammatory and Oxidative Stress Mechanisms in the Pathogenesis of Parkinson’s Disease: Focus on Astrocytes
Niranjan, R. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8483-x · Cited by 338
α‐Synuclein pathology of the spinal and peripheral autonomic nervous system in neurologically unimpaired elderly subjects
Bloch, A., Probst, A., Bissig, H., Adams, H., & Tolnay, M. (2006) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2006.00727.x · Cited by 337
α‐Synuclein pathology does not predict extrapyramidal symptoms or dementia
Parkkinen, L., Kauppinen, T., Pirttilä, T., Autere, J. M., & Alafuzoff, I. I. (2004) · Annals of Neurology · doi:10.1002/ana.20321 · Cited by 328
Clinical heterogeneity of α‐synuclein gene duplication in Parkinson's disease
Nishioka, K., Hayashi, S., Farrer, M. J., Singleton, A., Yoshino, H., Imai, H., Kitami, T., Sato, K., Kuroda, R., Tomiyama, H., et al. (2005) · Annals of Neurology · doi:10.1002/ana.20753 · Cited by 319
Gastrointestinal manifestations in Parkinson's disease: Prevalence and occurrence before motor symptoms
Cersosimo, M. G., Raina, G. B., Pecci, C., Pellene, A., Calandra, C. R., Gutiérrez, C., Micheli, F. E., & Benarroch, E. E. (2013) · Journal of Neurology · doi:10.1007/s00415-012-6801-2 · Cited by 314
Progression of intestinal permeability changes and alpha-synuclein expression in a mouse model of Parkinson's disease
Kelly, L. P., Carvey, P. M., Keshavarzian, A., Shannon, K. M., Shaikh, M., Bakay, R. A. E., & Kordower, J. H. (2014) · Movement Disorders · doi:10.1002/mds.25736 · Cited by 308
Parkinson's Disease: The Dual Hit Theory Revisited
Hawkes, C. H., Del Tredici, K., & Braak, H. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04365.x · Cited by 303
Lewy pathology in the submandibular gland of individuals with incidental Lewy body disease and sporadic Parkinson’s disease
Tredici, K. D., Hawkes, C. H., Ghebremedhin, E., & Braak, H. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0665-2 · Cited by 303
Activation of MyD88-dependent TLR1/2 signaling by misfolded α-synuclein, a protein linked to neurodegenerative disorders
Daniele, S. G., Béraud, D., Davenport, C., Cheng, K., Yin, H., & Maguire-Zeiss, K. A. (2015) · Science Signaling · doi:10.1126/scisignal.2005965 · Cited by 303
Transplanted dopaminergic neurons develop PD pathologic changes: A second case report
Kordower, J. H., Chu, Y., Hauser, R. A., Olanow, C. W., & Freeman, T. B. (2008) · Movement Disorders · doi:10.1002/mds.22369 · Cited by 301
Gastrointestinal dysfunction in Parkinson's disease
Pfeiffer, R. F. (2011) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2010.08.003 · Cited by 298
Pathological correlates of gastrointestinal dysfunction in Parkinson's disease
Cersosimo, M. G., & Benarroch, E. E. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.10.014 · Cited by 294
Factors predictive of the development of levodopa‐induced dyskinesia and Wearing‐Off in Parkinson's disease
Rajput, A. H. (2013) · Movement Disorders · doi:10.1002/mds.25800 · Cited by 291
Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated α-synuclein gene mutations precede central nervous system changes
Kuo, Y., Li, Z., Jiao, Y., Gaborit, N., Pani, A. K., Orrison, B. M., Bruneau, B. G., Giasson, B. I., Smeyne, R. J., Gershon, M. D., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq038 · Cited by 289
Increased susceptibility to sporadic Parkinson's disease by a certain combined ?-synuclein/apolipoprotein E genotype
Krüger, R., Vieira-Saecker, A. M. M., Kuhn, W., Berg, D., M�ller, T., K�hnl, N., Fuchs, G., Storch, A., Hungs, M., Woitalla, D., et al. (1999) · Annals of Neurology · doi:10.1002/1531-8249(199905)45:5 · Cited by 281
The prion hypothesis in Parkinson's disease: braak to the future
Visanji, N. P., Brooks, P. L., Hazrati, L.-N., & Lang, A. E. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-2 · Cited by 278
Toll-Like Receptor 4 Promotes α-Synuclein Clearance and Survival of Nigral Dopaminergic Neurons
Stefanova, N., Fellner, L., Reindl, M., Masliah, E., Poewe, W., & Wenning, G. K. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.04.013 · Cited by 272
The second brain and Parkinson’s disease
Lebouvier, T., Chaumette, T., Paillusson, S., Duyckaerts, C. J., Varannes, S. B. D., Neunlist, M., & Derkinderen, P. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06873.x · Cited by 271
Alpha-synuclein cell-to-cell transfer and seeding in grafted dopaminergic neurons in vivo
Angot, E., Steiner, J. A., Lema Tomé, C. M., Ekström, P., Mattsson, B., Björklund, A., & Brundin, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039465 · Cited by 270
Comparative effects of very low-carbohydrate, high-fat and high-carbohydrate, low-fat weight-loss diets on bowel habit and faecal short-chain fatty acids and bacterial populations
Brinkworth, G. D., Noakes, M., Clifton, P. M., & Bird, A. R. (2009) · British Journal Of Nutrition · doi:10.1017/s0007114508094658 · Cited by 269
Chronic rotenone exposure reproduces Parkinson's disease gastrointestinal neuropathology
Drolet, R. E., Cannon, J. R., Montero, L. M., & Greenamyre, J. T. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.06.017 · Cited by 262
Neuroinflammation in Alzheimer's Disease and Parkinson's Disease: Are Microglia Pathogenic in Either Disorder?
Rogers, J., Mastroeni, D., Leonard, B., Joyce, J., & Grover, A. (2007) · International Review of Neurobiology · doi:10.1016/s0074-7742(07)82012-5 · Cited by 260
Microglial phenotypes and toll-like receptor 2 in the substantia nigra and hippocampus of incidental Lewy body disease cases and Parkinson’s disease patients
Doorn, K. J., Moors, T., Drukarch, B., van de Berg, W. D., Lucassen, P. J., & van Dam, A.-M. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0090-1 · Cited by 254
Lewy body-related ?-synucleinopathy in the aged human brain
Jellinger, K. A. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-004-0138-7 · Cited by 253
Patterns and stages of α-synucleinopathy
ZACCAI, J. H., Brayne, C., McKeith, I. G., Matthews, F. E., & Ince, P. G. (2008) · Neurology · doi:10.1212/01.wnl.0000306697.48738.b6 · Cited by 249
Inflammation and α-Synuclein’s Prion-like Behavior in Parkinson's Disease—Is There a Link?
Tomé, C. M. L., Tyson, T., Rey, N. L., Grathwohl, S. A., Britschgi, M., & Brundin, P. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8267-8 · Cited by 247
Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease
ANDERSON, G., Noorian, A. R., Taylor, G. T., Anitha, M., BERNHARD, D., SRINIVASAN, S., & GREENE, J. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.05.010 · Cited by 245
The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson's disease: a critical analysis of α‐synuclein staging
Kalaitzakis, M. E., Graeber, M. B., Gentleman, S., & Pearce, R. K. B. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00923.x · Cited by 243
Degeneration of Cardiac Sympathetic Nerve Begins in the Early Disease Process of Parkinson’s Disease
Orimo, S., Takahashi, A., Uchihara, T., Mori, F., Kakita, A., Wakabayashi, K., & Takahashi, H. (2007) · Brain Pathology · doi:10.1111/j.1750-3639.2006.00032.x · Cited by 243
A critical reappraisal of current staging of Lewy-related pathology in human brain
Jellinger, K. A. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0406-y · Cited by 240
Progressive Aggregation of Alpha-Synuclein and Selective Degeneration of Lewy Inclusion-Bearing Neurons in a Mouse Model of Parkinsonism
Osterberg, V. R., Spinelli, K. J., Weston, L. J., Luk, K. C., Woltjer, R. L., & Unni, V. K. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.01.060 · Cited by 240
Olfactory bulb α-synucleinopathy has high specificity and sensitivity for Lewy body disorders
Beach, T. G., White, C. L., Hladik, C. L., Sabbagh, M. N., Connor, D. J., Shill, H. A., Sue, L. I., Sasse, J., Bachalakuri, J., Henry-Watson, J., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0450-7 · Cited by 237
Behavioral and immunohistochemical effects of chronic intravenous and subcutaneous infusions of varying doses of rotenone
Fleming, S. M. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.01.023 · Cited by 230
Seeking a Mechanism for the Toxicity of Oligomeric α-Synuclein
Hall‐Roberts, H., & Brown, D. R. (2015) · Biomolecules · doi:10.3390/biom5020282 · Cited by 222
Characterization of Lewy body pathology in 12‐ and 16‐year‐old intrastriatal mesencephalic grafts surviving in a patient with Parkinson's disease
Li, J., Englund, E. M., Widner, H., Rehncrona, S., Björklund, A., Lindvall, O., & Brundin, P. (2010) · Movement Disorders · doi:10.1002/mds.23012 · Cited by 221
α-Synuclein Alters Toll-Like Receptor Expression
Béraud, D., Twomey, M. A., Bloom, B., Mittereder, A., Ton, V., Neitzke, K., Chasovskikh, S., Mhyre, T. R., & Maguire‐Zeiss, K. A. (2011) · Frontiers in Neuroscience · doi:10.3389/fnins.2011.00080 · Cited by 203
Bowel movement frequency in late‐life and incidental Lewy bodies
Abbott, R. D., Ross, G. W., Petrovitch, H., Tanner, C. M., Davis, D. G., Masaki, K., Launer, L. J., Curb, J. D., & White, L. R. (2007) · Movement Disorders · doi:10.1002/mds.21560 · Cited by 203
α-Synuclein pathology in Parkinson’s and Alzheimer’s disease brain: incidence and topographic distribution—a pilot study
Jellinger, K. A. (2003) · Acta Neuropathologica · doi:10.1007/s00401-003-0725-y · Cited by 201
Association of olfactory dysfunction with incidental Lewy bodies
Ross, G. W., Abbott, R. D., Petrovitch, H., Tanner, C. M., Davis, D. G., Nelson, J. R., Markesbery, W. R., Hardman, J. M., Masaki, K., Launer, L. J., et al. (2006) · Movement Disorders · doi:10.1002/mds.21076 · Cited by 194
Exogenous α-synuclein induces toll-like receptor 4 dependent inflammatory responses in astrocytes
Rannikko, E. H., Weber, S. S., & Kahle, P. J. (2015) · BMC Neuroscience · doi:10.1186/s12868-015-0192-0 · Cited by 185
Poor and protracted myelination as a contributory factor to neurodegenerative disorders
Braak, H., & Tredici, K. D. (2003) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.04.001 · Cited by 179
An association study of asthma and total serum immunoglobin E levels for Toll‐like receptor polymorphisms in a Japanese population
Noguchi, E., Nishimura, F., Fukai, H., Kim, J. K., Ichikawa, K., Shibasaki, M., & Arinami, T. (2004) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2004.01839.x · Cited by 176
Transfer of host-derived alpha synuclein to grafted dopaminergic neurons in rat
Kordower, J. H., Dodiya, H. B., Kordower, A. M., Terpstra, B. T., Paumier, K. L., Madhavan, L., Sortwell, C. E., Steece‐Collier, K., & Collier, T. J. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.05.001 · Cited by 176
Delayed gastric emptying and enteric nervous system dysfunction in the rotenone model of Parkinson's disease
Greene, J. G., Noorian, A. R., & Srinivasan, S. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.04.023 · Cited by 165
Toll like receptor 4 mediates cell death in a mouse MPTP model of Parkinson disease
Noelker, C., Morel, L., Lescot, T., Osterloh, A., Alvarez-Fischer, D., Breloer, M., Henze, C., Depboylu, C., Skrzydelski, D., Michel, P. P., et al. (2013) · Scientific Reports · doi:10.1038/srep01393 · Cited by 164
Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease
Milber, J. M., Noorigian, J. V., Morley, J. F., Petrovitch, H., White, L., Ross, G. W., & Duda, J. E. (2012) · Neurology · doi:10.1212/wnl.0b013e318278fe32 · Cited by 163
The medical treatment of Parkinson disease from James Parkinson to George Cotzias
Fahn, S. (2014) · Movement Disorders · doi:10.1002/mds.26102 · Cited by 162
Disentangling the Relationship between Lewy Bodies and Nigral Neuronal Loss in Parkinson's Disease
Parkkinen, L., O’Sullivan, S. S., Collins, C., Petrie, A., Holton, J. L., Révész, T., & Lees, A. J. (2011) · Journal of Parkinson s Disease · doi:10.3233/jpd-2011-11046 · Cited by 159
Toll-like receptor expression in the blood and brain of patients and a mouse model of Parkinson's disease
Drouin-Ouellet, J., St-Amour, I., Saint-Pierre, M., Lamontagne-Proulx, J., Kriz, J., Barker, R. A., & Cicchetti, F. (2015) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu103 · Cited by 153
Brain stem pathology in Parkinson's disease: An evaluation of the Braak staging model
Kingsbury, A. E., Bandopadhyay, R., Silveira‐Moriyama, L., Ayling, H., Kallis, C., Sterlacci, W., Maeir, H., Poewe, W. H., & Lees, A. J. (2010) · Movement Disorders · doi:10.1002/mds.23305 · Cited by 152
Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] α-synuclein mice
Lindström, V., Fagerqvist, T., Nordström, E. K. L., Eriksson, F., Lord, A., Tucker, S. M., Andersson, J., Johannesson, M., Schell, H., Kahle, P. J., et al. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.009 · Cited by 138
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Regional Distribution of α-Synuclein Pathology in Unimpaired Aging and Alzheimer Disease
Parkkinen, L., Soininen, H. S., & Alafuzoff, I. I. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.4.363 · Cited by 129
Signs of Degeneration in 12–22-Year Old Grafts of Mesencephalic Dopamine Neurons in Patients with Parkinson's Disease
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Mice overexpressing wild‐type human alpha‐synuclein display alterations in colonic myenteric ganglia and defecation
Wang, L., Magen, I., Yuan, P. Q., Subramaniam, S., Richter, F., Chesselet, M. ‐., & Taché, Y. (2012) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2012.01974.x · Cited by 118
Enteric glial cells: New players in Parkinson's disease?
Clairembault, T., Leclair‐Visonneau, L., Neunlist, M., & Derkinderen, P. (2015) · Movement Disorders · doi:10.1002/mds.25979 · Cited by 117
Heritability of Parkinson disease in Swedish twins: a longitudinal study
Wirdefeldt, K., Gatz, M., Reynolds, C. A., Prescott, C. A., & Pedersen, N. L. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.02.017 · Cited by 113
Alpha-synuclein overexpressing transgenic mice show internal organ pathology and autonomic deficits
Hallett, P. J., McLean, J. R., Kartunen, A., Langston, J. W., & Ole Isacson, A. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.04.009 · Cited by 111
Interactions between misfolded protein oligomers and membranes: A central topic in neurodegenerative diseases?
Andreasen, M., Lorenzen, N., & Otzen, D. E. (2015) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2015.01.018 · Cited by 109
Lewy body pathology in fetal grafts
Chu, Y., & Kordower, J. H. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05229.x · Cited by 104
Axonal transport of synucleins is mediated by all rate components
Jensen, P. H., Li, J., Dahlström, A. B., & Dotti, C. G. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00754.x · Cited by 102
MPTP-induced parkinsonism extends to a subclass of TH-positive neurons in the gut
Natale, G., Kastsiushenka, O., Fulceri, F., Ruggieri, S. A., Paparelli, A., & Fornai, F. (2010) · Brain Research · doi:10.1016/j.brainres.2010.07.076 · Cited by 101
Preconditioning of Microglia by α-Synuclein Strongly Affects the Response Induced by Toll-like Receptor (TLR) Stimulation
Roodveldt, C., Labrador‐Garrido, A., González‐Rey, E., Lachaud, C. C., Guilliams, T., Fernández-Montesinos, R., Benitez-Rondan, A., Robledo, G., Hmadcha, A., Delgado, M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079160 · Cited by 99
Alpha‐synuclein pathology in the olfactory pathways of dementia patients
Hubbard, P. S., Esiri, M. M., Reading, M. C., McShane, R. H., & Nagy, Z. (2007) · Journal of Anatomy · doi:10.1111/j.1469-7580.2007.00748.x · Cited by 98
The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson's disease
Attems, J., & Jellinger, K. A. (2008) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2008.00937.x · Cited by 96
Mitochondrial Dysfunction and α -Synuclein Synaptic Pathology in Parkinson’s Disease: Who’s on First?
Zaltieri, M., Longhena, F., Pizzi, M., Missale, C., Spano, P., & Bellucci, A. (2015) · Parkinson s Disease · doi:10.1155/2015/108029 · Cited by 95
Age-related loss of dorsal vagal neurons in Parkinson's disease
Gai, W., Blumbergs, P. C., Geffen, L. B., & Blessing, W. W. (1992) · Neurology · doi:10.1212/wnl.42.11.2106 · Cited by 85
Alpha-synuclein transgenic mice display age-related slowing of gastrointestinal motility associated with transgene expression in the vagal system
Noorian, A. R., Rha, J., Annerino, D. M., Bernhard, D., Taylor, G. M., & Greene, J. G. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.06.005 · Cited by 80
The pathology roadmap in Parkinson disease
Surmeier, D. J., & Sulzer, D. (2013) · Prion · doi:10.4161/pri.23582 · Cited by 74
Inflammation and neurodegeneration: the story ‘retolled’
Drouin‐Ouellet, J., & Cicchetti, F. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.07.002 · Cited by 71
Controversies over the staging of α-synuclein pathology in Parkinson’s disease
Kalaitzakis, M. E., Graeber, M. B., Gentleman, S. M., & Pearce, R. K. B. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0381-3 · Cited by 68
A not entirely benign procedure: progression of Parkinson’s disease
Tredici, K. D., & Braak, H. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0355-5 · Cited by 67
Parkinson's disease with involvement of the parasympathetic ganglia
Takeda, S., Yamazaki, K., Miyakawa, T., & Arai, H. (1993) · Acta Neuropathologica · doi:10.1007/bf00369454 · Cited by 63
β1-integrin-dependent migration of microglia in response to neuron-released α-synuclein
Kim, C., Cho, E.-D., Kim, H.-K., You, S., Lee, H.-J., Hwang, D., & Lee, S. (2014) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.6 · Cited by 60
Considerations on the role of environmental toxins in idiopathic Parkinson’s disease pathophysiology
Pan-Montojo, F. J., & Reichmann, H. (2014) · Translational Neurodegeneration · doi:10.1186/2047-9158-3-10 · Cited by 54
Extensive aggregation of α-synuclein and tau in juvenile-onset neuroaxonal dystrophy: an autopsied individual with a novel mutation in the PLA2G6 gene-splicing site
Riku, Y., Ikeuchi, T., Yoshino, H., Mimuro, M., Mano, K., Goto, Y., Hattori, N., Sobue, G., & Yoshida, M. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-12 · Cited by 41
Gut Microbiota, Diet, and Heart Disease
Wong, J. M., Esfahani, A., Singh, N., Villa, C., Mirrahimi, A., Jenkins, D. J. A., & Kendall, C. W. C. (2012) · Journal of AOAC International · doi:10.5740/jaoacint.sge_wong · Cited by 35
Elevated neuronal α-synuclein promotes microglia activation after spinal cord ischemic/reperfused injury
Qiao, H., Zhang, Q., Yuan, H., Li, Y., Wang, D., Wang, R., & He, X. (2015) · Neuroreport · doi:10.1097/wnr.0000000000000406 · Cited by 25
TLR9 −1237 T/C and TLR2 −194 to −174 del polymorphisms and the risk of Parkinson’s disease in the Greek population: a pilot study
Kalinderi, K., Bostantjopoulou, S., Katsarou, Z., & Fidani, L. (2012) · Neurological Sciences · doi:10.1007/s10072-012-1106-x · Cited by 22
Evidence against a reliable staging system of α‐synuclein pathology in Parkinson's disease
Kalaitzakis, M. E., Graeber, M. B., Gentleman, S., & Pearce, R. K. B. (2009) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2008.00998.x · Cited by 19
Good vibrations with deep brain stimulation
Williams, Z. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4007 · Cited by 13
Colonic Neuropathology is Independent of Olfactory Dysfunction in Parkinson's Disease
Lebouvier, T., Pouclet, H., Coron, E., Chauviré-Drouard, A., Nguyen, J., Roy, M., Vavasseur, F., Varannes, S. B. D., Damier, P., Neunlist, M., et al. (2011) · Journal of Parkinson s Disease · doi:10.3233/jpd-2011-11061 · Cited by 10

Research works printed but not linked: 1

Piccini, 1999, The role of inheritance in sporadic Parkinson’s disease: evidence from a longitudinal study of dopaminergic function in twins, Ann Neurol, 45, 577, 10.1002/1531-8249(199905)45:5577::AID-ANA53.0.CO;2-O · DOI

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Authors: Rietdijk, C. D., Perez-Pardo, P., Garssen, J., van Wezel, R. J. A., & Kraneveld, A. D.
Affiliations: Utrecht University (NL)
Corresponding author: Kraneveld, Aletta D.
ORCID: Garssen, Johan
Kraneveld, Aletta D.
Venue: Frontiers in Neurology
Publisher: Frontiers Media SA
Published: 2017-02-13
Volume: 8
Pages: 37-37
ISSN: 1664-2295 (ISSN-L)
DOI: 10.3389/fneur.2017.00037
PMC: PMC5304413
OpenAlex: W2588841770
Cited by: 395
References: 153
Citations by year: 2026: 41 · 2025: 56 · 2024: 65 · 2023: 43 · 2022: 50 · 2021: 50 · 2020: 30 · 2019: 32 · 2018: 18 · 2017: 10
FWCI: 3.27
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Neurology (publishedVersion, cc-by)
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PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
University of Twente Research Information (submittedVersion, other-oa)
Radboud Repository (Radboud University) (submittedVersion, other-oa)
Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Radboud Repository (Radboud University) (submittedVersion)
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: Parkinson's disease, Braak hypothesis, Lewy body pathology, sporadic Parkinson's disease, gut-brain axis, alpha-synuclein toxicity, Lewy bodies, neurodegeneration, early-onset Parkinson's disease

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Exploring Braak’s Hypothesis of Parkinson’s Disease

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