Evidence map›Paper›PMID 36351406›Full record

ArticleCell reports2022

Mesoscale connections and gene expression empower whole-brain modeling of α-synuclein spread, aggregation, and decay dynamics.

Ehsan Dadgar-Kiani, Gregor Bieri, Ronald Melki, Aaron D Gitler, Jin Hyung Lee

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.Movement disorders : official journal of the Movement Disorder Society · 2024
    Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Ehsan Dadgar-KianiDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Gregor BieriDepartment of Genetics, Stanford University, Stanford, CA 94305, USA.
Ronald MelkiInstitut François Jacob, MIRCen, CEA and Laboratory of Neurodegenerative Diseases, CNRS, 92265 Fontenay-Aux-Roses, France.
Aaron D GitlerDepartment of Genetics, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: agitler@stanford.edu.
Jin Hyung LeeDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA. Electronic address: ljinhy@stanford.edu.

Funding

Innovating Yeast and Human Genetics Approaches to Define Mechanisms of Neurodegenerative DiseaseR35NS097263 · NINDS · STANFORD UNIVERSITY · PI GITLER, AARON D. · 2017 to 2024
$8.6M
VECTOR COREP30NS069375 · NINDS · STANFORD UNIVERSITY · PI SHAMLOO, MEHRDAD · 2011 to 2019
$6.3M
Defining Cell Type Specific Contributions to fMRI SignalsRF1MH114227 · NIMH · STANFORD UNIVERSITY · PI LEE, JIN HYUNG · 2017 to 2017
$3.7M
Dynamic regulation of whole brain circuit function by basal ganglia pathwaysR01NS091461 · NINDS · STANFORD UNIVERSITY · PI LEE, JIN HYUNG · 2015 to 2019
$2.4M
Deconstructing Arousal Regulation Circuits for Optimal DBS Therapy DesignR01NS087159 · NINDS · STANFORD UNIVERSITY · PI LEE, JIN HYUNG · 2014 to 2018
$1.9M
Direct Visualization of Cell-Type Specific AD Networks for Drug DevelopmentRF1AG047666 · NIA · STANFORD UNIVERSITY · PI LEE, JIN HYUNG · 2014 to 2014
$1.8M
NIA NIH HHS RF1 AG047666NIMH NIH HHS RF1 MH114227NINDS NIH HHS P30 NS069375NINDS NIH HHS R01 NS087159NINDS NIH HHS R01 NS091461NINDS NIH HHS R35 NS097263
6 · The paper itself

Abstract

An emerging view regarding neurodegenerative diseases is that discreet seeding of misfolded proteins leads to widespread pathology. However, the mechanisms by which misfolded proteins seed distinct brain regions and cause differential whole-brain pathology remain elusive. We used whole-brain tissue clearing and high-resolution imaging to longitudinally map pathology in an α-synuclein pre-formed fibril injection model of Parkinson's disease. Cleared brains at different time points of disease progression were quantitatively segmented and registered to a standardized atlas, revealing distinct phases of spreading and decline. We then fit a computational model with parameters that represent α-synuclein pathology spreading, aggregation, decay, and gene expression pattern to this longitudinal dataset. Remarkably, our model can generalize to predicting α-synuclein spreading patterns from several distinct brain regions and can even estimate their origins. This model empowers mechanistic understanding and accurate prediction of disease progression, paving the way for the development and testing of therapeutic interventions.

Indexed as

alpha-SynucleinSynucleinopathiesBrainDisease ProgressionGene ExpressionHumansalpha-Synucleinaggregationalpha-synucleinCP: Neuroscienceneurodegenerative diseaseParkinson's diseasePrion-likespreadingwhole-brain pathology

Identifiers

PMID36351406
PMCPMC10840492

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.