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Spread of aggregates after olfactory bulb injection of α-synuclein fibrils is associated with early neuronal loss and is reduced long term
Open accessAbstract
Parkinson's disease is characterized by degeneration of substantia nigra dopamine neurons and by intraneuronal aggregates, primarily composed of misfolded α-synuclein. The α-synuclein aggregates in Parkinson's patients are suggested to first appear in the olfactory bulb and enteric nerves and then propagate, following a stereotypic pattern, via neural pathways to numerous regions across the brain. We recently demonstrated that after injection of either mouse or human α-synuclein fibrils into the olfactory bulb of wild-type mice, α-synuclein fibrils recruited endogenous α-synuclein into pathological aggregates that spread transneuronally to over 40 other brain regions and subregions, over 12 months. We previously reported the progressive spreading of α-synuclein aggregates, between 1 and 12 months following α-synuclein fibril injections, and now report how far the pathology has spread 18- and 23-month post-injection in this model. Our data show that between 12 and 18 months, there is a further increase in the number of brain regions exhibiting pathology after human, and to a lesser extent mouse, α-synuclein fibril injections. At both 18 and 23 months after injection of mouse and human α-synuclein fibrils, we observed a reduction in the density of α-synuclein aggregates in some brain regions compared to others at 12 months. At 23 months, no additional brain regions exhibited α-synuclein aggregates compared to earlier time points. In addition, we also demonstrate that the induced α-synucleinopathy triggered a significant early neuron loss in the anterior olfactory nucleus. By contrast, there was no loss of mitral neurons in the olfactory bulb, even at 18 month post-injection. We speculate that the lack of continued progression of α-synuclein pathology is due to compromise of the neural circuitry, consequential to neuron loss and possibly to the activation of proteolytic mechanisms in resilient neurons of wild-type mice that counterbalances the spread and seeding by degrading pathogenic α-synuclein.
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Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,893
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
Stages in the development of Parkinson’s disease-related pathology
Braak, H., Ghebremedhin, E., Rüb, U., Bratzke, H., & Del Tredici, K. (2004) · Cell and Tissue Research · doi:10.1007/s00441-004-0956-9 · Cited by 2,689
Cellular Scaling Rules for the Brains of Marsupials: Not as “Primitive” as Expected
Santos, S. E. D., Porfírio, J., Cunha, F., Manger, P. R., Tavares, W. C., Pessôa, L. M., Raghanti, M. A., Sherwood, C. C., & Herculano‐Houzel, S. (2017) · Brain Behavior and Evolution · doi:10.1159/000452856 · Cited by 2,652
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
Self-citationNeuN, a neuronal specific nuclear protein in vertebratesxs
Mullen, R. J., Buck, C. R., & Smith, A. M. (1992) · Development · doi:10.1242/dev.116.1.201 · Cited by 2,351
α-Synuclein is phosphorylated in synucleinopathy lesions
Fujiwara, H., Hasegawa, M., Dohmae, N., Kawashima, A., Masliah, E., Goldberg, M. S., Shen, J., Takio, K., & Iwatsubo, T. (2002) · Nature Cell Biology · doi:10.1038/ncb748 · Cited by 2,174
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
Depletion of microglia and inhibition of exosome synthesis halt tau propagation
Asai, H., Ikezu, S., Tsunoda, S., Medalla, M., Luebke, J., Haydar, T., Wolozin, B., Butovsky, O., Kügler, S., & Ikezu, T. (2015) · Nature Neuroscience · doi:10.1038/nn.4132 · Cited by 1,591
Differential projections of the infralimbic and prelimbic cortex in the rat
Vertes, R. P. (2004) · Synapse · doi:10.1002/syn.10279 · Cited by 1,550
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- 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 VMY, Adler CH, Beach TG, Trojanowski JQ (2016) Pathological α-synuclein distribution in subjects with coincident Alzheimer’s and Lewy body pathology. Acta Neuropathol 131:393–409. https://doi.org/10.1007/s00401-015-1526-9 · DOI · Paper page
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Items 201–214 of 214
Schaser, A. J., Stackhouse, T. L., Weston, L. J., Kerstein, P. C., Osterberg, V. R., López, C. S., Dickson, D. W., Luk, K. C., Meshul, C. K., Woltjer, R. L., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12891231
Self-citationEvaluating Odor Selectivity in $$\alpha $$-Synucleinopathy: ML-Based Odor Profiling
Mattjie, C., Ravazio, R., Mitchell, E., Bestwick, J. P., Kupssinskü, L. S., Noyce, A. J., Schuh, A. F. S., & Barros, R. C. (2026) · Lecture notes in computer science · doi:10.1007/978-3-032-15990-8_13
Étude de la propagation prion-like de l'alpha-synucléine dans des réseaux de neurones reconstruits
Courte, J. (2019) · theses.fr (ABES) · doi:10.70675/95ccfbd6zedb2z4a1bz8024zb46a3ec60ebf
Étude moléculaire de l'inflammation chronique dans la maladie de Parkinson
Compagnion, A. (2019) · theses.fr (ABES) · doi:10.70675/04ca138dz3131z4e24z884czbba2f7954a99
Développement et caractérisation de nouveaux modèles murins de maladie à corps de Lewy
Schueller, E. (2020) · theses.fr (ABES) · doi:10.70675/4a313736z3f42z4d92zb1c1ze3cbd7bbe9f6
Engineered Exosomes: Innovative Strategies for Precision Drug Delivery in Parkinson’s Disease
Yuan, X., Wang, C., Yan, J., Wang, J., Li, F., You, Y., & Qi, Z. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05898-6
Vaidya, B., Li, Y., Kim, Y. D., Osterman, C., Revelli, J., & Zoghbi, H. Y. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.18.726024
Delva, A., Joza, S., Tremblay, C., Vo, A., Filiatrault, M., Carrier, M., Taylor, J., O'Brien, J. T., Firbank, M., Thomas, A. J., et al. (2026) · Journal of Biomedical Science · doi:10.1186/s12929-026-01267-6
Al‐Shami, A. S., & Anwar, M. M. (2026) · Inflammopharmacology · doi:10.1007/s10787-026-02285-4
Akanchise, T., Luo, F., Angelov, B., Deng, Y., Fujino, T., & Angelova, A. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02897-w
Guatteo, E., Romano, M. Z., Berretta, N., Ruggiero, M., Santoro, A., Mazzeo, F., & Meccariello, R. (2026) · Microplastics · doi:10.3390/microplastics5030166
LeeBae, J., Bopp, V., Goreth, A., Grozdanov, V., Engels, Z., Kühlwein, J. K., Gazzola, E., Rombach, D., Meier, L., Dimou, L., et al. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00046-9
Sharma, M., Sharma, N., Soni, J., Uttarkar, M., Kučerová, J., Outeiro, T. F., Rektorová, I., & Khairnar, A. (2026) · npj Parkinson s Disease · doi:10.1038/s41531-026-01593-4
Silvestri, F., Bronzato, E., Scambi, I., Arietti, V., Sacchetto, L., Mariotti, R., Zanusso, G., Bongianni, M., & Turano, E. (2026) · Cells · doi:10.3390/cells15191824
Metadata
- Authors
- Rey, N. L., George, S., Steiner, J. A., Madaj, Z., Luk, K. C., Trojanowski, J. Q., Lee, V. M.-Y., & Brundin, P.
- Affiliations
- Van Andel Institute (US)
- University of Pennsylvania (US)
- Corresponding author
- Rey, Nolwen L.
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2017-12-05
- Volume
- 135
- Issue
- 1
- Pages
- 65-83
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC5756266
- OpenAlex
- W2774883898
- Cited by
- 215
- References
- 77
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 17 · 2023: 18 · 2022: 25 · 2021: 41 · 2020: 39 · 2019: 29 · 2018: 10 · 2017: 2
- FWCI
- 15.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Acta Neuropathologica (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Van Andel Research Institute
- Peter C. and Emajean Cook Foundation
- National Institutes of Health (1R01DC016519-01, 5R21NS093993-02)
- Penn Morris K. Udall Parkinson's disease Research Center of Excellence (P50 NS053488)
- Penn Morris K. Undall Parkinson's Research Center of Excellence (P50 NS053488)
- Penn AD Core center (P30 AG10124, P01 AG17586)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- alpha-synuclein fibrils, Parkinson's disease, olfactory bulb, transneuronal spread, synucleinopathies, neuronal loss, anterior olfactory nucleus, mitral cells, substantia nigra, neurodegeneration
- MeSH terms
- Animals, Biological Transport, Brain, Disease Models, Animal, DNA-Binding Proteins, Female, Humans, Mice, Inbred C57BL, Neurons, Olfactory Bulb, Recombinant Proteins, tau Proteins, Cell Death, Disease Progression, Neurodegenerative Diseases, alpha-Synuclein, Protein Aggregation, Pathological
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