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Exploring Braak’s Hypothesis of Parkinson’s Disease
Open accessAbstract
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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“GI symptoms may predate motor features by years, consistent with the concept that α-synuclein pathology can involve the ENS and vagal/brainstem autonomic nuclei early in disease (Rietdijk et al., 2017; Travagli et al., 2020).”
From Autonomic nervous system and gastrointestinal manifestations with an emphasis on gastric dysfunction (2026) · cites this paper as Rietdijk et al., 2017
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Adaptive deep brain stimulation in Parkinson's disease
de Neeling, M. G. J., Keulen, B. J., Stam, M. J., van Wijk, B. C. M., & Beudel, M. (2026) · The Lancet · doi:10.1016/s0140-6736(25)02274-3 · Cited by 7
Parkinson’s Disease–An Introduction
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Alpha-synuclein and tau are abundantly expressed in the ENS of the human appendix and monkey cecum
Zinnen, A. D., Vichich, J. M., Metzger, J. M., Gambardella, J. C., Bondarenko, V., Simmons, H. A., & Emborg, M. E. (2022) · PLoS ONE · doi:10.1371/journal.pone.0269190 · Cited by 7
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Anti-Inflammatory Effect of Traditional Chinese Medicine on the Concept of Mind-Body Interface
Tsai, S.-T., Nithiyanantham, S., Satyanarayanan, S. K., & Su, K. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-981-19-7376-5_19 · Cited by 7
Etiology and pathogenesis of Parkinson disease
Jankovic, J. J., Hallett, M., Okun, M. S., Comella, C., Fahn, S., & Goldman, J. G. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-31071-0.00005-6 · Cited by 8
Dietary Factors Affect Brain Iron Accumulation and Parkinson’s Disease RiskPreprint
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“This score is differentially associated with a higher risk of PD in individuals with and without hemochromatosis, where individuals with hemochromatosis and very high HB-PVS show increased PD risk, whereas in individuals without hemochromatosis, a lower HB-PVS compared to other healthy subjects is…”
The role of the gut microbiome in Parkinson’s disease
Metcalfe‐Roach, A., & Finlay, B. B. (2025) · Future Neurology · doi:10.1080/14796708.2025.2494981 · Cited by 6
Chen, H., Cheng, X., Pan, X., Yu, Y., Chen, L., Fu, Y., & Pan, X. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1608031 · Cited by 6
The ketogenic diet in Parkinson’s disease: a potential therapeutic strategy
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Zhang, J., Zhou, C., Xiao, X., Chen, W., Jiang, Y., Zhu, R., & Xin, T. (2022) · International Journal for Numerical Methods in Biomedical Engineering · doi:10.1002/cnm.3642 · Cited by 6
“The stimulation parameters can be adjusted according to the selected stimulation mode (single-stage or bipolar) and stimulation contacts.(4) At present, the international clinical evaluation of PD is mostly based on the unified Parkinson's disease rating scale (UPDRs), which mainly evaluates the exercise status and da…”
BackgroundTargeting the microbiota-mitochondria crosstalk in neurodegeneration with senotherapeutics
Homolak, J. (2023) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2023.02.018 · Cited by 8
Sebastian, I. A., Kate, M. P., Khatter, H., Singh, B., & Pandian, J. D. (2022) · Annals of Indian Academy of Neurology · doi:10.4103/aian.aian_289_22 · Cited by 6
“The presence of AD even in the earlier stages of Parkinson’s disease finds explanation in the “central” Braak theory[23] which postulates the spread of Lewy body pathology via the olfactory bulb and vagus nerve to the substantia nigra and central nervous system.”
BackgroundBidirectional relationship between olfaction and Parkinson’s disease
Kim, J. J., Bandrés‐Ciga, S., Heilbron, K., Aslibekyan, S. W., Auton, A., Babalola, E., Bell, R. K., Bielenberg, J., Bowes, J., Bryc, K., et al. (2024) · npj Parkinson s Disease · doi:10.1038/s41531-024-00838-4 · Cited by 5
Probiotic: A Gut Microbiota-Based Therapeutic Approaches for the Treatment of Parkinson’s Disease
Rout, M., Prusty, S. K., & Kar, D. M. (2024) · Current Clinical Pharmacology · doi:10.2174/0127724328332572241219102122 · Cited by 5
Role of neuron specific enolase as a biomarker in Parkinson’s disease
Dutta, R. (2021) · Journal of Neuroscience and Neurological Disorders · doi:10.29328/journal.jnnd.1001052 · Cited by 5
Calcium Channels and Selective Neuronal Vulnerability in Parkinson’s Disease
Liss, B., & Surmeier, D. J. (2022) · Springer eBooks · doi:10.1007/978-3-031-08881-0_22 · Cited by 6
Recent advances in nanotechnology and its application for neuro-disease: a review
Radhakrishnan, K. G., Kumar, P. S., Rangasamy, G., Ankitha, K., Niyathi, V., Manivasagan, V., & Saranya, K. (2023) · Applied Nanoscience · doi:10.1007/s13204-023-02958-4 · Cited by 5
“There are estimates of heritability ranging from 27 to 34% in twin studies for Parkinson's disease to 22–27 percent in genetic (SNP-based) research (Huddleston et al. 2017; Rietdijk et al. 2017).”
BackgroundConcepts of Hypothesis Testing and Types of Errors
Ganeshpurkar, A., Maheshwari, R., Tekade, M., & Tekade, R. K. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-814421-3.00007-5 · Cited by 5
Zhang, J. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.968193 · Cited by 5
“Over the years, mounting evidence from clinical research has supported the Braak hypothesis (143).”
BackgroundCardiac sympathetic “morbidity” might reflect the neurobiology of early Parkinson’s disease
Yoo, S., Oh, Y., Ryu, D.-W., Ha, S., Lyoo, C. H., Kim, Y., Yoo, J.-Y., & Kim, J. (2023) · Journal of Neurology · doi:10.1007/s00415-023-12049-7 · Cited by 5
The impact of cardiovascular diseases and new gene variants in swaying Alzheimer’s disease
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Cannas, F., Kopeć, K. K., Zuddas, N., Marincola, F. C., Arcara, G., Loi, M., Mussap, M., & Fanos, V. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14176277 · Cited by 4
“The age range of participants varied across studies, typically including individuals in their mid-50s to late 60s, consistent with the epidemiology of Parkinson’s disease [1–4].”
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Noor, S. M., & Norazit, A. (2022) · Fisheries and aquatic sciences · doi:10.47853/fas.2022.e11 · Cited by 4
An Overview of Neurodegenerative Disorders
Mittal, P., & Agrawal, N. (2024) · Springer eBooks · doi:10.1007/978-981-97-4288-2_1 · Cited by 4
MRI Epicenters Differentiate Spatiotemporal Patterns of Neurodegeneration in Parkinson's Disease
Duanmu, X., Zhu, Z., Wen, J., Qin, J., Zheng, Q., Yuan, W., Jin, Y., Lu, N., Wang, L., Zhou, C., et al. (2025) · Advanced Science · doi:10.1002/advs.202511289 · Cited by 4
Interplay of alpha-synuclein pathology and gut microbiome in Parkinson’s disease
Srivastava, A., Kataria, A., Yadav, D. K., Han, I., & Choi, E. H. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91313-3.00003-9 · Cited by 4
Gut Microbes in Parkinson's Disease
Markidi, A., Elford, J. D., Berkers, C. R., Kraneveld, A. D., & Perez‐Pardo, P. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-99971-7.00002-3 · Cited by 4
Self-citationRadziwon, J., & Sławek, J. W. (2024) · Neurologia i Neurochirurgia Polska · doi:10.5603/pjnns.99592 · Cited by 4
“Despite recent opinions that this ascending pattern of pathological process does not represent all cases [2, 3], the experimental evidence supporting the concept of vagus vulnerability is growing.”
BackgroundOlfactory Network Disruptions as Mediators of Cognitive Impairment in De Novo Parkinson's Disease
Xing, Y., Zhou, H., Chen, S., Wang, Y., Ren, J., Cao, Y., Li, J., & Liu, W. (2025) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70198 · Cited by 4
“…pathological staging model, pathological changes in the brains of PD patients initially occur in olfactory-related regions, such as the olfactory bulb, anterior olfactory nucleus, and certain secondary olfactory structures [33, 34], explaining the common occurrence of OD in the early stage of PD.”
Mirab, F., Pirhaghi, M., Otzen, D. E., & Saboury, A. A. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2025.167862 · Cited by 4
Rethinking Parkinson Disease: Exploring Gut-Brain Interactions and the Potential Role of Exercise
Zapanta, K., Schroeder, E. T., & Fisher, B. E. (2022) · Physical Therapy · doi:10.1093/ptj/pzac022 · Cited by 5
Neuropathology of Circadian Alterations in Parkinson Disease
Fifel, K. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2018.3755 · Cited by 4
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“Aggregated α-synuclein spreads toward the CNS through the vagus nerve and reaches the substantia nigra and other brain regions (Rietdijk et al. 2017).”
Resting-State EEG Alpha Asymmetry as a Potential Marker of Clinical Features in Parkinson’s Disease
da Rocha, T. F., Costa, V., Camargo, L., Fernandes, E. B., & Gianlorenço, A. C. (2025) · Journal of Personalized Medicine · doi:10.3390/jpm15070291 · Cited by 3
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“Genetic anomalies are what lead to the family form [5].”
InfluentialThe Gut–Brain–Immune Axis: Multi-Omics Insights into Neurodegenerative and Metabolic Diseases
Khan, S.-U.-D., Chauhan, V., Chaudhary, A. A., & Khan, M. (2026) · Cells · doi:10.3390/cells15121089 · Cited by 3
“Gastrointestinal dysfunction, particularly constipation, is also recognized as an important https://doi.org/10.3390/cells15121089 prodromal feature of PD [44].”
InfluentialLiu, W., Zhou, W., Zhao, P., Wu, T., Gu, H., Li, Y., Zhong, C., Bai, H., Zhao, N., & Huang, X. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04076-w · Cited by 3
“Braak’s hypothesis states that sporadic PD is triggered by infection with specific pathogens, and pathologic spread starts from the olfactory bulb and spreads to the peripheral nerves of the gastrointestinal tract [28, 29].”
Depression is associated with the nonmotor symptoms of Parkinson's disease: A comparative analysis
Mayeli, M., Shafie, M., Shiravi, M., Parvar, T. A., Mirsepassi, Z., Rahiminejad, F., Sattarpour, R., & Aghamollaii, V. (2024) · Health Science Reports · doi:10.1002/hsr2.2106 · Cited by 3
“37,38 However, the exact etiology is yet not well understood.”
BackgroundParkinson’s disease: exploring the systemic immune mechanisms through molecular investigations
Mohan, M., Mannan, A., & Singh, T. G. (2025) · Inflammopharmacology · doi:10.1007/s10787-025-01816-9 · Cited by 3
“Braak’s hypothesis is one of the most pertinent hypotheses that suggest that a lesion in the enteric nervous system caused by pathogens can induce α-syn aggregation and then back-spread from the gut to the CNS via the vagus nerve (Rietdijk et al. 2017).”
Han, F., Liu, M., Jiao, Q., Du, X., Yan, C., Chen, X., & Jiang, H. F. (2025) · Neuroscience Bulletin · doi:10.1007/s12264-025-01509-x · Cited by 3
Screening for non-motor symptoms in Parkinson's disease using the NMSQuest scale
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Dietary interventions in Parkinson’s disease: An update
Pavan, S., Prabhu, A., Gorthi, S. P., Shetty, V., Rajesh, V., Hegde, A., & Ballal, M. (2022) · Biomedicine · doi:10.51248/.v42i3.1639 · Cited by 3
“The gastrointestinal tract and nasal cavity are the two main vulnerable sites for exposure to environmental toxins (1).”
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“…disorders interrelated to mitochondrial failings, the neurons show modifications in the oxidative phosphorylation, the homeostasis of intracellular ROS and the levels of calcium, as well as in the mitochondrial kinesis, mitophagy and fusion/fission dynamics (Burte et al., 2015; Ryan et al., 2015).”
BackgroundRole of the Intestinal Microbiota in the Molecular Pathogenesis of Atypical Parkinsonian Syndromes
Przewodowska, D., Alster, P., & Madetko‐Alster, N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26093928 · Cited by 4
“Through the promotion of regional inflammation and intestinal barrier disruption, these pathogens stimulate local α -synuclein accumulation, which then could be transported by the vagal nerve into the CNS [12].”
A Bayesian Network Model for the Parkinson’s Disease: A Study of Gene Expression Levels
Mestizo-Gutiérrez, S. L., Jácome-Delgado, J. A., Rosales-Morales, V. Y., Cruz-Ramírez, N., & Aranda-Abreu, G. E. (2019) · Studies in computational intelligence · doi:10.1007/978-3-030-06149-4_7 · Cited by 3
Microbiota-Brain-Gut Axis and Neurodegenerative Disorders
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Dietary and Environmental Risk Factors in Parkinson’s Disease and Alzheimer’s Disease
Madhaw, G., & Kumar, N. (2023) · Annals of Indian Academy of Neurology · doi:10.4103/aian.aian_82_23 · Cited by 3
“[10,11] Secondly, it has been suggested that the alpha‐synuclein from the enteric nervous system can reach the brain via the vagus nerve and dorsal motor nucleus of the vagus within the medulla oblongata.[12]”
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“…microbial products may trigger α -synuclein aggregates in the enteric nervous system, which propagate via the vagus nerve to the substantia nigra(Rietdijk et al., 2017), while gut-derived lipopolysaccharides (LPS) and inflammatory cytokines activate microglia, driving neuroinflammation and…”
Iyengar, A. S., Dunkley, P. R., & Dickson, P. W. (2025) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2025.578755 · Cited by 3
Staging and markers in Parkinson’s disease and Lewy body disorders: narrative review
Bougea, A. M. (2025) · Therapeutic Advances in Chronic Disease · doi:10.1177/20406223251381099 · Cited by 2
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Roseburia intestinalis Offers Vagus-Dependent Neuroprotection Against Parkinson’s Disease
Li, M., Wu, J., Xiang, J., Yang, Z., Wang, B., Li, P., Zheng, M., Li, Y., Shao, X., & He, L. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05707-0 · Cited by 2
“The Braak hypothesis proposes that α-synuclein pathology originates in the enteric nervous system and ascends via the vagus nerve to the dorsal motor nucleus, spreading caudo–rostrally from the brainstem to the substantia nigra and cortex [10].”
Bibliometric analysis of the pathogenesis of Parkinson's Disease
Feng, Y., Wang, K., Guo, X., Guo, H., & Gao, X. (2026) · Pathology - Research and Practice · doi:10.1016/j.prp.2026.156417 · Cited by 2
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Mante, N., Undale, V., Sanap, A. P., Bhonde, R. R., Kheur, S. M., Tambe, P., & Kharat, A. H. (2026) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2026.578911 · Cited by 2
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Targeting TLR4 in Parkinson's disease: mechanisms and therapeutic prospects
Dong, S., Lu, J., Wu, L., Wang, S., 宫玉波, Hu, J., Liu, Y., & Chen, X. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116780 · Cited by 2
LPS-Induced Neuroinflammation in Neurodegenerative Diseases: A Double-Edged Sword?
Mohammadi, A., Aghajan, A., Alipour, M., Ghorbani, A., Limoodehi, S. M., & Hedayati, M. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06004-6 · Cited by 2
“…LPS exposure drives dopaminergic neuronal loss and motor deficits in animal models [8], while clinical observations show that gastrointestinal symptoms, including constipation and dysphagia, often precede motor manifestations, supporting the notion of peripheral-to-central disease propagation [60].”
The role of alpha-sinuclein in the neurodegenerative process
Sobolev, V. B., & Худоерков, Р. М. (2019) · CLINICAL AND EXPERIMENTAL MORPHOLOGY · doi:10.31088/cem2019.8.3.5-12 · Cited by 2
“В обзорных статьях последних лет [11, 13] авторы на основании обобщенного материала пришли к выводу, что гипотеза Браака подтверждается и in vitro,”
InfluentialErnesto, J. T., Damásio, C. M., Gontijo, V. S., Gasparotto, J., & Viegas, C. (2023) · Exploration of Neuroprotective Therapy · doi:10.37349/ent.2023.00038 · Cited by 2
L’intestin, lanceur d’alerte, dans les prémices de la maladie de Parkinson
Hazart, D., Rolli‐Derkinderen, M., Delhomme, B., Derkinderen, P., Oheim, M., & Ricard, C. (2024) · médecine/sciences · doi:10.1051/medsci/2024082 · Cited by 2
Yoo, S., Ryu, D.-W., Oh, Y., Ha, S., Lyoo, C. H., & Kim, J. (2024) · Journal of Neurology · doi:10.1007/s00415-024-12586-9 · Cited by 2
“Extra-nigral sites, despite some controversies, have been described as the entrance and propagation sites, with particular emphasis on the olfactory route and the effects of swallowing nasal secretions [2–4].”
Roshni, J., Sivakumar, M., Ahmad, S. F., Al‐Mazroua, H. A., Kamath, S. M., & Ahmed, S. S. S. J. (2024) · Molecular Biotechnology · doi:10.1007/s12033-024-01262-y · Cited by 2
“Finally, the progression in Stages 5 and 6 covers the entire neocortical structure [10–12].”
Infection, Neuroinflammation and Interventions for Healthy Brain and Longevity
Fülöp, T., Ramassamy, C., Lacombe, G., Frost, E. H., Cohen, A. A., Rodrigues, S., Desroches, M., Hirokawa, K., Laurent, B., & Witkowski, J. M. (2024) · Healthy ageing and longevity · doi:10.1007/978-3-031-68513-2_12 · Cited by 2
Malvasi, M., Pascale, E., Locuratolo, N., Fattapposta, F., Pauletti, C., Finoia, M. G., Conti, M. E., & Pacella, E. (2025) · European Journal of Ophthalmology · doi:10.1177/11206721251335060 · Cited by 3
“39 According to the study of Tran KKN et al., 40 the retinal thickness of PD patients at the macular level, particularly in the temporal and inferior sectors in both eyes, was reduced in 100% of cases compared to control group values.”
Nakamura, K., Tagai, K., Shinotoh, H., Hirano, S., Kitamura, S., Endo, H., Takahata, K., Takado, Y., Zhang, M., Kawamura, K., et al. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251351220 · Cited by 2
“1,2 In addition, Alzheimer ’ s disease (AD) pathologies such as amyloid-β and tau depositions are often associated with LBD. 3,4 Within LBD, the incidence of amyloid-β pathology is higher in DLB, although amyloid deposition is also seen in PD. 5,6 It has been documented that amyloid-β accumulation…”
Jeong, S. H., Kim, S. H., Park, C. W., Lee, H. S., Lee, P. H., Kim, Y. J., Sohn, Y. H., Jeong, Y., & Chung, S. J. (2025) · Clinical Nuclear Medicine · doi:10.1097/rlu.0000000000005922 · Cited by 2
Wu, D., Jiang, Q., Shen, G., Gao, X., Liu, C., & Ye, W. (2025) · Annals of Nuclear Medicine · doi:10.1007/s12149-025-02112-w · Cited by 2
“These findings align with the Braak pathological staging model and prior imaging studies using high-affinity DAT tracers (e.g., β-CIT, FP-CIT) [10–13], supporting the potential role of putaminal asymmetry as a promising imaging marker for early dopaminergic degeneration.”
Yuluğ, B., Ozansoy, M., & Çankaya, Ş. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.257527 · Cited by 2
“These findings were also suggested with clinical studies showing that Lewy pathology is not a reliable indicator of PD cellular dysfunction in patients with specific PD-causing mutations (such as leucine-rich repeat kinase 2) (Burke et al., 2008; Rietdijk et al., 2017).”
BackgroundResultInfluentialA review on factors causing parkinson’s syndrome
Piramanayagam, S., & Selvaraj, S. (2018) · MOJ Proteomics & Bioinformatics · doi:10.15406/mojpb.2018.07.00243 · Cited by 2
Deep Brain Stimulation for Parkinson’s Disease
ten Brinke, T. R., Beudel, M., & de Bie, R. M. A. (2020) · Springer eBooks · doi:10.1007/978-3-030-36346-8_12 · Cited by 2
COVID-19: The cynosure of rise of Parkinson's disease
Kukkle, P. L. (2022) · International review of neurobiology · doi:10.1016/bs.irn.2022.06.007 · Cited by 1
Role of short-chain fatty acids in the pathogenesis of Parkinson’s disease
Вячеславович, К. И., Litvinenko, I., Родионов, Г. Г., Davydova, N. I., & Aleksanin, S. S. (2022) · Russian Military Medical Academy Reports · doi:10.17816/rmmar111854 · Cited by 1
Liu, Z., Lemus, J., Smirnova, I. V., & Liu, W. (2023) · Exploration of Neuroprotective Therapy · doi:10.37349/ent.2023.00049 · Cited by 1
Umbilical Cord-Derived Cells: Applications in Neurological Disorders
Vasques, J. F., Chimeli-Ormonde, L., Gubert, F., Méndez‐Otero, R., & Pimentel‐Coelho, P. M. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-15717-2.00003-2 · Cited by 1
MicroRNA-Targeted Gene Regulation in Salivary Gland Tissue of De Novo Parkinson’s Disease Patients
Choi, K. H., Kim, S., Jang, J., Ryu, D.-W., Oh, Y., & Kim, J. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04581-y · Cited by 1
How gut microbes affect Parkinson’s disease: an editorial
Nasir, R., Haseeb, A., Mustafa, M. S., Mussarat, A., Ali, L., Shafique, M. A., & Ahmed, K. A. H. M. (2025) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000003098 · Cited by 1
“Braak’s theory further supports this idea, proposing that these microorganisms enter the gastrointestinal tract and subsequently advance into the brain via the vagus nerve, contributing to the development of PD [ 2–4 ] .”
Verde, C. D., Jayanti, S. D., El-Khobar, K. E., Stanford, J. A., Tiribelli, C., & Gazzin, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26146881 · Cited by 3
“Intragastric rotenone has been used to test (with positive results) the Braak hypotheses that PD synucleinopathy starts in the enteric system [371] and reaches the brain through the vagus nerve where it propagates like a prion [35,38,372].”
InfluentialMicroRNAs and synaptic dysfunction in Parkinson’s disease
Ogwo, M. N., Sharma, B., Goyal, G., Lakshmanaswamy, R., & Kumar, S. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102673 · Cited by 1
“…of the enteric nervous system (ENS), which subsequently propagates by way of retrograde axonal transmission to the dorsal motor nucleus of the vagus nerve (DMX) and eventually to various regions of the CNS. 15,16 The pathogen was suggested to be a neurotropic virus with prion-like properties.”
Gut microbiota in regulation of neuromuscular coordination
Roy, S., Chakraborty, B., & Choudhury, L. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-33351-4.00024-6 · Cited by 1
Protein misfolding and neurodegeneration: Mechanisms, implications, and therapeutic strategies
Shah, A., Karthikeyan, T., Hashem, S., Kumar, R., Bhat, A. A., & Macha, M. A. (2025) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2025.08.012 · Cited by 2
A Study of Gene Expression Levels of Parkinson’s Disease Using Machine Learning
Mestizo-Gutiérrez, S. L., Jácome-Delgado, J. A., Cruz-Ramírez, N., Guerra‐Hernández, A., Torres-Sosa, J. A., Rosales-Morales, V. Y., & Aranda-Abreu, G. E. (2025) · BioMedInformatics · doi:10.3390/biomedinformatics5040060 · Cited by 1
“Parkinson’s disease (PD) is a neurodegenerative disorder primarily characterized by motor impairment resulting from the degeneration of dopaminergic neurons in the sub-stantia nigra (SN) located in the midbrain [1,2].”
Meimoun, N. S., Benji, S., Besharim, W. Z., Cantor, Y. Y., Carroll, E. S., Coplin, B. I., Davidovics, M. B., Gerber, M., Hirschprung, P. M., Jacobson, E. I., et al. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1534243 · Cited by 1
Unraveling the Link between Sleep Disturbances and Parkinson’s Disease: A Narrative Review
Cárdenas-Saénz, O., Macías-Ortíz, F. G., Becerra-Aguiar, N. N., Real, S. S. D., Orozco-Puga, P., Camacho-Ordóñez, A., & Rodríguez‐Violante, M. (2025) · Acta Neurologica Taiwanica · doi:10.4103/ant.ant-d-25-00003 · Cited by 2
Thatcher, T. B. C., Sharrad, S., & Bobrovskaya, L. (2026) · Neurological Sciences · doi:10.1007/s10072-025-08650-5 · Cited by 1
Eldesouki, M. H., Shaban, A. Y., Marey, M. M., Rabea, E. M., Helal, A., Seisa, M., Abdelhalim, O., Abosheaishaa, H. M., & Khalaf, M. M. (2026) · JGH Open · doi:10.1002/jgh3.70302 · Cited by 1
Examination of shared gut microbiome signatures in aging and Parkinson’s disease
Tng, T. J. W., Vanan, S., Tan, E.-K., Zeng, L., Goh, W. W. B., Wong, H. S., & Lim, K. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1745455 · Cited by 3
“…German pathologist Heiko Braak postulated that sporadic PD could develop from the spreading of these α -synuclein aggregates starting either from the nasal cavity or the gut before they infiltrate the brain (Rietdijk et al., 2017; Borghammer and Van Den Berge, 2019; Van Den Berge and Ulusoy, 2022).”
Gut, brain and the Glycocalyx: A portrait of Parkinsons disease
Ninham, B. W., Battye, M., & Carlin, M. R. (2026) · Advances in Colloid and Interface Science · doi:10.1016/j.cis.2026.103880 · Cited by 1
Cardona, E. A., Webber, C. J., Wu, Z., Bolton, B., Cenik, E. S., & Pierce-Shimomura, J. T. (2026) · Disease Models & Mechanisms · doi:10.1242/dmm.052469 · Cited by 1
“Neurodegenerative disorders such as Alzheimer ’ s disease (AD), Parkinson ’ s disease (PD) and frontotemporal lobar dementia (FTLD) present with characteristic spatiotemporal patterns of neuronal cell death (Braak and Braak, 1991; Lima-Silva et al., 2013; reviewed in Rietdijk et al., 2017).”
Immunotherapy in Neurodegenerative Disorders
Kamthe, D., Gosavi, N., & Nikam, V. S. (2020) · Springer eBooks · doi:10.1007/978-981-15-9038-2_5 · Cited by 2
The influence of parasomnia on clinical and functional characteristics of extrapyramidal disorders
Doronina, K. S., Illarioshkin, S. N., & Doronina, O. B. (2021) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro202112109113 · Cited by 1
The gut microbiome in neurodegenerative disorders
Abughazaleh, S. J., Euers, L. A., & Quigley, E. M. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821039-0.00006-x · Cited by 1
Cognitive Decline in Parkinson's Disease: Theories and Implications for Rehabilitation
Brown, K. A., Summers Dale, K. L., & Spencer Kristie, A. (2022) · International Journal of Neurodegenerative Disorders · doi:10.23937/2643-4539/1710022 · Cited by 1
Waack, A. L., Maddens, M. E., Maddens, N. J., Kuhlman, A., & Staudt, M. D. (2023) · Case Reports in Neurology · doi:10.1159/000531570 · Cited by 1
“The progression of disease re fl ects the hypothesis that PD pathology begins in the optic bulb and enteric nervous system, with subsequent retrograde migration to the central nervous system via the olfactory and vagus nerves, respectively [4, 5].”
BackgroundInfluentialMajeed, O. A., AlLami, M. Q., & AlGawwam, G. (2024) · Journal of Angiotherapy · doi:10.25163/angiotherapy.859642 · Cited by 1
Understanding Parkinson's Disease: A Basic Overview
Anderson, R. L., Choo, A., Sharrad, S., & Withey, R. (2023) · Australasian Journal of Neuroscience · doi:10.21307/ajon-2023-012 · Cited by 1
When immune cells are coached by intestinal microbiota
Méli, A. C. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvz346 · Cited by 2
L-Theanine: Neuroprotective against Trichloroethylene-induced Parkinsons disease hallmarks
Justin, S. (2020) · Journal of Toxicology and Environmental Health Sciences · doi:10.5897/jtehs2020.0468 · Cited by 1
“In accordance with Braak’s hypothesis, TCE-induced PD is hypothesized to progress in living organisms through the ingestion of TCEcontaminated drinking water and inhalation of TCEcontaminated air through the gastrointestinal and olfactory tract, respectively (Braak et al., 2003; Khare et al., 2018; Rietdijk et al., 20…”
BackgroundInfluential
Metadata
- 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.
- Venue
- Frontiers in Neurology
- Publisher
- Frontiers Media SA
- Published
- 2017-02-13
- Volume
- 8
- Pages
- 37-37
- ISSN
- 1664-2295 (ISSN-L)
- 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)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- 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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