The DOI matches its Crossref record; 152 of the 153 references it cites were found in a registry or an index.
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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Cites
Staging of brain pathology related to sporadic Parkinson’s disease
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Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
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Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis
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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
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The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice
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“Dietary components and dietary patterns have a considerable effect on the composition of the gut microbiome (66).”
BackgroundThe 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
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
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
Research works printed but not linked: 1
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Cited by
Sorted by citations
Microbiota-Brain-Gut Axis and Neurodegenerative Diseases
Quigley, E. M. M. (2017) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-017-0802-6 · Cited by 804
The anatomical basis for transcutaneous auricular vagus nerve stimulation
Butt, M. F., Albusoda, A., Farmer, A. D., & Aziz, Q. (2019) · Journal of Anatomy · doi:10.1111/joa.13122 · Cited by 616
“…are selectively vulnerable to the early pathophysiological processes of Alzheimer’s (Parvizi et al. 2001) and Parkinson’s diseases (Braak et al. 2003; Rietdijk et al. 2017), thus a method to assess the function of vagal nuclei, potentially by employing tVNS, may be used to detect these…”
MethodThe genetics of Parkinson disease
Deng, H., Wang, P., & Jankovic, J. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2017.12.007 · Cited by 530
“the Braak hypothesis has been criticized by some scientists (Rietdijk et al., 2017).”
BackgroundMaiti, P., Manna, J., & Dunbar, G. L. (2017) · Translational Neurodegeneration · doi:10.1186/s40035-017-0099-z · Cited by 557
“According to Braak’s hypothesis, SNCA, bacteria, or viruses can travel via the olfactory tract and into the Vegas nerve to the medala and spread throughout the CNS, which can responsible initiate sporadic PD [155].”
BackgroundMicrobiome–microglia connections via the gut–brain axis
Abdel-Haq, R., Schlachetzki, J. C. M., Glass, C. K., & Mazmanian, S. K. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20180794 · Cited by 471
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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