Evidence map›Paper›PMID 40855085›Full record

ArticleNPJ Parkinson's disease2025

Novel in situ seeding immunodetection assay uncovers neuronal-driven alpha-synuclein seeding in Parkinson's disease.

Maria Otero-Jimenez, Marcelina J Wojewska, Simona Jogaudaite, David Miller, Sandra Gray-Rodriguez, Grainne C Geoghegan, Laura Abelleira-Hervas, Tim James Viney, Barbara Sarkany, Djordje Gveric and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ Parkinson's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Maria Otero-JimenezDepartment of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Marcelina J Wojewska *Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Simona Jogaudaite *Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
David MillerImperial College Advanced Hackspace, Imperial College London, London, UK.
Sandra Gray-RodriguezDepartment of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Grainne C GeogheganDepartment of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Laura Abelleira-HervasDepartment of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Tim James VineyDepartment of Pharmacology, University of Oxford, Oxford, UK.
Barbara SarkanyDepartment of Pharmacology, University of Oxford, Oxford, UK.
Djordje GvericDepartment of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Steve GentlemanDepartment of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Javier Alegre-AbarrateguiDepartment of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK. j.alegre@imperial.ac.uk.

Funding

MRC MR/Z504518/1
6 · The paper itself

Abstract

Aggregates of alpha-synuclein (α-syn) propagate through template-induced misfolding in people with Parkinson's disease (PD) and Multiple System Atrophy (MSA). Prion-like seeding is crucial in disease initiation and progression, representing a major target for disease-modifying therapies. The detection of α-syn seeding with seeding amplification assays (SAAs) has remarkable diagnostic and research potential. However, current SAAs rely on bulk tissue homogenates or fluids, losing critical spatial and cellular resolution. Here, we report our novel in situ seeding immunodetection (isSID) assay that enables the visualization of seeding with unprecedented morphological detail in intact biological tissue. Using the isSID assay, we confirm seeding activity in α-syn aggregates in PD, MSA, and other proteinopathies, while uncovering neuron-driven seeding preceding the clinical symptom onset in PD. Our findings provide new fundamental insights into the pathogenesis underlying neurodegeneration and establish an invaluable tool for studying protein aggregation dynamics, with potential applications in biomarker discovery, diagnostics, and therapeutics.

Identifiers

PMID40855085
PMCPMC12379234

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.