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Record W4402409330 · doi:10.1007/s00415-024-12647-z

GFAP and NfL as fluid biomarkers for clinical disease severity and disease progression in multiple system atrophy (MSA)

2024· article· en· W4402409330 on OpenAlexaff
Sabrina Katzdobler, Georg Nübling, Martin Klietz, Urban M. Fietzek, Carla Palleis, Alexander Bernhardt, Florian Wegner, Meret K. Huber, Sophia Rogozinski, Luisa‐Sophie Schneider, Eike Jakob Spruth, Aline Beyle, Ina R. Vogt, Moritz Brandt, Niels Hansen, Wenzel Glanz, Kathrin Brockmann, Annika Spottke, Daniel C. Hoffmann, Oliver Peters, Josef Priller, Jens Wiltfang, Emrah Düzel, Anja Schneider, Björn Falkenburger, Thomas Klockgether, Thomas Gasser, Brigitte Nuscher, Christian Haass, Günter U. Höglinger, Johannes Levin

Bibliographic record

VenueJournal of Neurology · 2024
Typearticle
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsIONICS Mass Spectrometry (Canada)
FundersAnton and Petra Ehrmann-StiftungDeutsches Zentrum für Neurodegenerative ErkrankungenDeutsche Forschungsgemeinschaft
KeywordsBiomarkerMedicineInternal medicineNeurologyPathologyAtrophyDiseaseReceiver operating characteristicGlial fibrillary acidic proteinOncologyAstrocytosisGastroenterologyBiologyImmunohistochemistryPsychiatry

Abstract

fetched live from OpenAlex

BACKGROUND: Multiple system atrophy (MSA), an atypical parkinsonian syndrome, is a rapidly progressive neurodegenerative disease with currently no established fluid biomarkers available. MSA is characterized by an oligodendroglial α-synucleinopathy, progressive neuronal cell loss and concomitant astrocytosis. Here, we investigate glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as fluid biomarkers for differential diagnosis, assessment of clinical disease severity and prediction of disease progression in MSA. METHODS: GFAP and NfL levels were analyzed in plasma and CSF samples of 47 MSA patients as well as 24 Parkinson's disease (PD) and 25 healthy controls (HC) as reference cohorts. In MSA, biomarker levels were correlated to baseline and longitudinal clinical disease severity (UMSARS scores). RESULTS: In MSA, GFAP levels in CSF and plasma predicted baseline clinical disease severity as indicated by UMSARS scores, while NfL levels predicted clinical disease progression as indicated by longitudinal changes in UMSARS scores. Cross-sectionally, NfL levels in CSF and plasma were significantly elevated in MSA compared to both PD and HC. Receiver operating curves (ROC) indicated high diagnostic accuracy of NfL for distinguishing MSA from PD (CSF: AUC = 0.97, 95% CI 0.90-1.00; plasma: AUC = 0.90, 95% CI 0.81-1.00). DISCUSSION: In MSA, GFAP shows promise as novel biomarker for assessing current clinical disease severity, while NfL might serve as biomarker for prediction of disease progression and differential diagnosis of MSA against PD.

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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.060
Threshold uncertainty score0.411

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
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 head0.036
GPT teacher head0.358
Teacher spread0.322 · 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

Citations22
Published2024
Admission routes1
Has abstractyes

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