Evidence map›Paper›PMID 41206373›Full record

ArticleActa neuropathologica2025

Co-infection with two α-synuclein strains reveals novel synergistic interactions.

Sara A M Holec, Chase R Khedmatgozar, Shelbe J Schure, Jason C Bartz, Amanda L Woerman

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Sara A M Holec *Department of Microbiology, Immunology, & Pathology and Prion Research Center, Colorado State University, 300 West Lake Street, Fort Collins, CO, 80521, USA.
Chase R Khedmatgozar *Department of Microbiology, Immunology, & Pathology and Prion Research Center, Colorado State University, 300 West Lake Street, Fort Collins, CO, 80521, USA.
Shelbe J SchureDepartment of Microbiology, Immunology, & Pathology and Prion Research Center, Colorado State University, 300 West Lake Street, Fort Collins, CO, 80521, USA.
Jason C BartzDepartment of Microbiology, Immunology, & Pathology and Prion Research Center, Colorado State University, 300 West Lake Street, Fort Collins, CO, 80521, USA.
Amanda L WoermanDepartment of Microbiology, Immunology, & Pathology and Prion Research Center, Colorado State University, 300 West Lake Street, Fort Collins, CO, 80521, USA. amanda.woerman@colostate.edu.

Funding

Effect of Agent and Host Factors on Alpha-Synuclein Strain PathogenesisR01NS121294 · NINDS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI Amanda L. Woerman · 2022 to 2026
$2.9M
A Novel Gene Therapy Approach to Prevent Alpha-synuclein Misfolding in Multiple System AtrophyR21NS127002 · NINDS · COLORADO STATE UNIVERSITY · PI WOERMAN, AMANDA L. · 2023 to 2024
$422k
A transcriptomics-based approach to identify quantitative biomarkers for multiple system atrophyF31NS139652 · NINDS · COLORADO STATE UNIVERSITY · PI Chase Reza Khedmatgozar · 2024 to 2026
$86k
NINDS NIH HHS F31 NS139652NINDS NIH HHS F31NS139652NINDS NIH HHS R01 NS121294NINDS NIH HHS R01NS121294NINDS NIH HHS R21 NS127002
6 · The paper itself

Abstract

In synucleinopathies, the protein α-synuclein misfolds into Lewy bodies (LBs) in patients with Lewy body disease (LBD) or into glial cytoplasmic inclusions (GCIs) in patients with multiple system atrophy (MSA). The ability of a single misfolded protein to cause disparate diseases is explained by the prion strain hypothesis, which argues that protein conformation is a major determinant of disease. We recently reported the unexpected finding of a novel α-synuclein strain in a Parkinson's disease with dementia patient sample containing GCI-like co-pathology along with widespread LB pathology, which led us to question if two α-synuclein strains can interact with one another in a patient and, if so, can strain competition occur. To test this possibility, we used the strain interference model developed in the prion field, in which a slower replicating strain-in this study, mouse-passaged MSA-is used to compete with a faster replicating strain-here, recombinant preformed fibrils (PFFs)-following sciatic nerve (sc.n.) inoculation. Unexpectedly, we found that PFFs generated using the same method differed in their ability to neuroinvade following sc.n. inoculation based on α-synuclein monomer source. Using a PFF preparation that does spread from the periphery, we conducted strain competition studies by first injecting TgM83

Indexed as

alpha-SynucleinCoinfectionMultiple System AtrophySynucleinopathiesAnimalsDisease Models, AnimalHumansMiceMice, Inbred C57BLSciatic Nervealpha-SynucleinLewy body diseasesMultiple system atrophyNeuroinvasionPreformed fibrilsStrain collusionStrain competition

Identifiers

PMID41206373
PMCPMC12596409

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.