Evidence map›Paper›PMID 33682732›Full record

ReviewJournal of Parkinson's disease2021

The α-Synuclein Origin and Connectome Model (SOC Model) of Parkinson's Disease: Explaining Motor Asymmetry, Non-Motor Phenotypes, and Cognitive Decline.

Per Borghammer

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of Parkinson's disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
144citing papers in PubMed, 4 pooled it
16.8field-weighted citation impact, top 1% of its field
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

144 citing papers in PubMed, 4 syntheses or guidelines pooled it, 234 citations in OpenAlex.

  1. Pooled it
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  4. Impact of aging on animal models of Parkinson's disease.Frontiers in aging neuroscience · 2022
    Pooled it
  5. Review
  6. Greater Motor and Nonmotor Burden at Diagnosis Is Associated With Amyloid Copathology in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  7. An exploratoryEuropean journal of nuclear medicine and molecular imaging · 2026
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  18. Is motor asymmetry a predictor of non-motor outcomes in Parkinson's disease?Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
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  20. Article

84 more citing papers are in PubMed but not listed here.

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

1 author at 1 institution in 1 country.

Per BorghammerDepartment of Nuclear Medicine & PET, Aarhus University Hospital, Aarhus, Denmark.
Aarhus University Hospital · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A new model of Parkinson's disease (PD) pathogenesis is proposed, the α-Synuclein Origin site and Connectome (SOC) model, incorporating two aspects of α-synuclein pathobiology that impact the disease course for each patient: the anatomical location of the initial α-synuclein inclusion, and α-synuclein propagation dependent on the ipsilateral connections that dominate connectivity of the human brain. In some patients, initial α-synuclein pathology occurs within the CNS, leading to a brain-first subtype of PD. In others, pathology begins in the peripheral autonomic nervous system, leading to a body-first subtype. In brain-first cases, it is proposed that the first pathology appears unilaterally, often in the amygdala. If α-synuclein propagation depends on connection strength, a unilateral focus of pathology will disseminate more to the ipsilateral hemisphere. Thus, α-synuclein spreads mainly to ipsilateral structures including the substantia nigra. The asymmetric distribution of pathology leads to asymmetric dopaminergic degeneration and motor asymmetry. In body-first cases, the α-synuclein pathology ascends via the vagus to both the left and right dorsal motor nuclei of the vagus owing to the overlapping parasympathetic innervation of the gut. Consequently, the initial α-synuclein pathology inside the CNS is more symmetric, which promotes more symmetric propagation in the brainstem, leading to more symmetric dopaminergic degeneration and less motor asymmetry. At diagnosis, body-first patients already have a larger, more symmetric burden of α-synuclein pathology, which in turn promotes faster disease progression and accelerated cognitive decline. The SOC model is supported by a considerable body of existing evidence and may have improved explanatory power.

Indexed as

Cognitive DysfunctionConnectomeParkinson DiseaseSynucleinopathiesalpha-SynucleinDopamineHumansPhenotypealpha-SynucleinDopaminealpha-synucleinautonomic nervous systemconnectomeetiologyParkinson’s diseasepathogenesis

Identifiers

PMID33682732
PMCPMC8150555
OpenAlexW3134318550

What OpenQuestion holds

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LicenceCC BY-NC
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.