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Record W4414416008 · doi:10.1016/j.ebiom.2025.105925

α-Synuclein seed amplification assay positivity beyond synucleinopathies

2025· article· en· W4414416008 on OpenAlexaff
Ivan Martinez-Valbuena, Sarah Fullam, Seán O’Dowd, Maria Carmela Tartaglia, Gábor G. Kovács

Bibliographic record

VenueEBioMedicine · 2025
Typearticle
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsToronto Western Hospital
FundersMichael J. Fox Foundation for Parkinson's Research
KeywordsSynucleinopathiesDiseaseCorticobasal degenerationProtein foldingCerebrospinal fluid

Abstract

fetched live from OpenAlex

Neurodegenerative diseases are increasingly recognized as complex disorders involving multiple protein pathologies, with α-synuclein frequently observed beyond classical synucleinopathies such as Parkinson's disease and multiple system atrophy. Recent advances in seed amplification assays (SAAs) have enabled the highly sensitive and specific detection of misfolded α-synuclein in vivo, particularly in cerebrospinal fluid (CSF). This review focuses on CSF-based α-synuclein SAAs and their application in detecting co-pathology across non-synucleinopathies, including Alzheimer's disease, progressive supranuclear palsy, corticobasal syndrome, idiopathic normal pressure hydrocephalus, and traumatic brain injury. Evidence indicates a role for α-synuclein in clinical heterogeneity and disease progression. Emerging diagnostic frameworks increasingly support integrating co-pathologies into classification and therapeutic strategies. Addressing key knowledge gaps, such as α-synuclein interactions with other protein pathologies, and current limitations of α-syn SAA, such as the lack of quantification of misfolded α-synuclein seeds, will refine precision medicine and improve outcomes for patients with neurodegenerative diseases.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.734
Threshold uncertainty score0.769

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.272
Teacher spread0.263 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations8
Published2025
Admission routes1
Has abstractyes

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