Cited by 215Parkinson's Disease Mechanisms and TreatmentsAlzheimer's disease research and treatmentsNuclear Receptors and Signaling

Spread of aggregates after olfactory bulb injection of α-synuclein fibrils is associated with early neuronal loss and is reduced long term

Open access
Rey, Nolwen L., George, Sonia, Steiner, Jennifer A., Madaj, Zachary, Luk, Kelvin C., Trojanowski, John Q., Lee, Virginia M.-Y., Brundin, Patrik·2018·Acta Neuropathologica

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s00401-017-1792-9

Cites

77 of 78 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. [70]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 Neuropathologica 131 393 409 10.1007/s00401-015-1526-9 26721587 PMC4754135 · DOI · Paper page

Cited by

Sorted by citations

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.
Venue
Acta Neuropathologica
Published
2017-12-05
Volume
135
Issue
1
Pages
65-83
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
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
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 › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review