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Record W4403597760 · doi:10.1093/brain/awae329

Neurodegenerative fluid biomarkers are enriched in human cervical lymph nodes

2024· article· en· W4403597760 on OpenAlexfundno aff
Adam Al‐Diwani, Nicholas M. Provine, Andrew G. Murchison, Rhiannon Laban, Owen Swann, Ivan Koychev, Fintan Sheerin, Sandro Dá Mesquita, Amanda Heslegrave, Henrik Zetterberg, Paul Klenerman, Sarosh R. Irani

Bibliographic record

VenueBrain · 2024
Typearticle
Languageen
FieldNeuroscience
TopicCerebrospinal fluid and hydrocephalus
Canadian institutionsnot available
FundersInstitute on Aging, College of Medicine, University of FloridaH2020 Marie Skłodowska-Curie ActionsNIHR Oxford Biomedical Research CentreUCLH Biomedical Research CentreHORIZON EUROPE Framework ProgrammeNational Institutes of HealthOlav Thon StiftelsenDementias Platform UKUK Dementia Research InstituteNorges IdrettshøgskoleMedical Research CouncilCure Alzheimer's FundDepartment of Health and Social CareMedical Research Council CanadaFamiljen Erling-Perssons StiftelseHjärnfondenEuropean CommissionUniversity of OxfordWellcome TrustUniversity College LondonAcademy of Medical SciencesHorizon 2020 Framework ProgrammeNational Institute on Handicapped ResearchFondation pour la Recherche MédicaleNational Institute on AgingNational Institute for Health and Care ResearchEU Joint Programme – Neurodegenerative Disease ResearchVetenskapsrådetBMA Foundation for Medical ResearchGlaucoma Research FoundationMayo ClinicNHS Innovation AcceleratorAlzheimer's Drug Discovery FoundationWellcomeAlzheimer's AssociationStiftelsen för Gamla TjänarinnorBrightFocus Foundation
KeywordsCervical lymph nodesLymphPathologyMedicineNeuroscienceBiologyCancerInternal medicine

Abstract

fetched live from OpenAlex

In animal models, brain neurodegeneration biomarkers drain into cervical lymph nodes (CLNs), and this drainage function is reduced with ageing. If this occurred in humans, CLNs may provide a readily accessible measure of this aspect of protein clearance. We tested this hypothesis in people using ultrasound-guided fine needle aspiration. We measured amyloid-beta 40 and 42, phosphorylated tau 181 (pTau181), glial fibrillary acidic protein and neurofilament light using single molecule array in CLN aspirates and plasma from: (i) a discovery cohort of 25 autoimmune patients; and (ii) plasma, CLNs and capillary blood in four healthy volunteers, an optimization cohort. Ultrasound-guided fine needle aspiration was well-tolerated by all participants. In both cohorts, all biomarkers were detected in all plasma and CLN samples, other than neurofilament light (8/17 of discovery cohort). CLN biomarker concentrations were significantly greater than plasma concentrations for all except neurofilament light, most markedly for pTau181 (266-fold; P < 0.02), whose CLN concentrations decreased with age (Spearman r = -0.66, P = 0.001). This study presents the first evidence that neurodegenerative biomarkers are detectable in human CLNs. Raised CLN:plasma biomarker ratios suggest their concentration in CLNs may offer a distinct compartment for minimally-invasive measurement of brain clearance and lymphatic drainage, with potential applicability to study of ageing and future clinical trials.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.226
Threshold uncertainty score0.703

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 head0.029
GPT teacher head0.293
Teacher spread0.264 · 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 designBench or experimental
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

Citations24
Published2024
Admission routes1
Has abstractyes

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