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Record W4386698139 · doi:10.1038/s41467-023-41122-y

CSF proteome profiling reveals biomarkers to discriminate dementia with Lewy bodies from Alzheimer´s disease

2023· article· en· W4386698139 on OpenAlexfundno aff
Marta del Campo, Lisa Vermunt, Carel F.W. Peeters, Anne Sieben, Yanaika S. Hok‐A‐Hin, Alberto Lleó, Daniel Alcolea, Mirrelijn M. van Nee, Sebastiaan Engelborghs, Juliette L. van Alphen, Sanaz Arezoumandan, Alice Chen‐Plotkin, David J. Irwin, Wiesje M. van der Flier, Afina W. Lemstra, Charlotte E. Teunissen

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsnot available
FundersNational Institute of Environmental Health SciencesNational Institute of Neurological Disorders and StrokeNational Institute on AgingInstituto de Salud Carlos IIIEuropean Regional Development FundAvid RadiopharmaceuticalsAllerganGenentechCentro de Investigación Biomédica en Red sobre Enfermedades NeurodegenerativasH. Lundbeck A/SServierPfizerBiogenAlzheimer NederlandZonMwNeurocrine BiosciencesUniversity of PennsylvaniaW. Garfield Weston FoundationCelgeneSanofiComunidad de MadridVerily Life SciencesTeva Pharmaceutical IndustriesHealth~HollandSun PharmaVoyager TherapeuticsBristol-Myers SquibbEli Lilly and Company
KeywordsDementia with Lewy bodiesBiomarkerProteomeDementiaMedicineAlzheimer's diseaseDiseaseCerebrospinal fluidPathologyFrontotemporal dementiaMultiplexBioinformaticsOncologyInternal medicineBiologyGenetics

Abstract

fetched live from OpenAlex

Diagnosis of dementia with Lewy bodies (DLB) is challenging and specific biofluid biomarkers are highly needed. We employed proximity extension-based assays to measure 665 proteins in the cerebrospinal fluid (CSF) from patients with DLB (n = 109), Alzheimer´s disease (AD, n = 235) and cognitively unimpaired controls (n = 190). We identified over 50 CSF proteins dysregulated in DLB, enriched in myelination processes among others. The dopamine biosynthesis enzyme DDC was the strongest dysregulated protein, and could efficiently discriminate DLB from controls and AD (AUC:0.91 and 0.81 respectively). Classification modeling unveiled a 7-CSF biomarker panel that better discriminate DLB from AD (AUC:0.93). A custom multiplex panel for six of these markers (DDC, CRH, MMP-3, ABL1, MMP-10, THOP1) was developed and validated in independent cohorts, including an AD and DLB autopsy cohort. This DLB CSF proteome study identifies DLB-specific protein changes and translates these findings to a practicable biomarker panel that accurately identifies DLB patients, providing promising diagnostic and clinical trial testing opportunities.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
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 head0.060
GPT teacher head0.370
Teacher spread0.311 · 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 source (direct Gemma or distilled Codex), 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

Citations71
Published2023
Admission routes1
Has abstractyes

Explore more

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