Evidence map›Paper›PMID 40681493›Full record

ArticleNature communications2025

Synaptic enrichment of pSer129 alpha-synuclein correlates with dopaminergic denervation in early-stage Parkinson's disease.

Irene Frigerio, Martino L Morella, Amber B Winkelaar, Danai T Vorgia, John Jp Brevé, Walter A Boiten, Bram L van der Gaag, Ismael L Calandri, Allert J Jonker, Henk W Berendse and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
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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

14 authors.

Irene FrigerioDepartment of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands. i.frigerio@amsterdamumc.nl.ORCID http://orcid.org/0000-0003-1780-2862
Martino L MorellaDepartment of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.ORCID http://orcid.org/0000-0003-1046-1698
Amber B WinkelaarDepartment of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Danai T VorgiaDepartment of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.ORCID http://orcid.org/0009-0006-3926-9148
John Jp BrevéDepartment of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Walter A BoitenDepartment of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Bram L van der GaagDepartment of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Ismael L CalandriDepartment of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Allert J JonkerDepartment of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Henk W BerendseAmsterdam Neuroscience, Neurodegeneration, Amsterdam, Netherlands.
Daniel MonaRoche Pharma Research and Early Development; Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.
Markus BritschgiRoche Pharma Research and Early Development; Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0001-6151-4257
Laura E JonkmanDepartment of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.ORCID http://orcid.org/0000-0003-1479-3649
Wilma Dj van de BergDepartment of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.ORCID http://orcid.org/0000-0002-6175-5357

Funding

Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation) 022468Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation) 17253
6 · The paper itself

Abstract

In Parkinson's disease (PD), α-synuclein aggregation in striatal synapses is hypothesised to trigger a cascade of events leading to synaptic loss and cortical Lewy body (LB) pathology. Using multiplex immunofluorescence and confocal microscopy on 69 brains spanning Braak stages 0-6-including controls, incidental LB disease (iLBD), and PD-we show that phosphorylated (pSer129) α-synuclein is enriched in putaminal dopaminergic synapses already in early disease stages, and associates with dopaminergic terminal loss. C-terminally truncated (CTT122) α-synuclein shows a similar trend in later stages. Enrichment of pSer129 and CTT122 α-synuclein in cortical glutamatergic synapses in the putamen occurs prior to LB appearance in cortical regions, supporting the theory of α-synuclein retrograde transport from synapse to cell body. Using AlphaLISA, we confirm that isolated PD putaminal synaptosomes contain higher pSer129 α-synuclein protein levels compared to controls. These findings suggest that synaptic enrichment of pSer129 α-synuclein occurs in early PD, possibly contributing to dopaminergic denervation and cortical LB pathology.

Indexed as

alpha-SynucleinDopamineDopaminergic NeuronsParkinson DiseaseSynapsesAgedAged, 80 and overFemaleHumansLewy BodiesMaleMiddle AgedPhosphorylationPutamenSynaptosomesalpha-SynucleinDopamineSNCA protein, human

Identifiers

PMID40681493
PMCPMC12274443

What OpenQuestion holds

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Registered trials

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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.