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Record W4390198333 · doi:10.1002/alz.081939

Synapse dysfunction and astrocyte reactivity are associated independently of amyloid‐β and tau pathologies

2023· article· en· W4390198333 on OpenAlexaffabout
Francieli Rohden, Bruna Bellaver, Pâmela C.L. Ferreira, Cristiano Schaffer Aguzzoli, Firoza Z Lussier, Carolina Soares, Guilherme Povala, João Pedro Ferrari‐Souza, Hussein Zalzale, Douglas Teixeira Leffa, Sarah Abbas, Arlec Cabrera, Peter Charles Lemaire, Cécile Tissot, Joseph Therriault, Stijn Servaes, Jenna Stevenson, Nesrine Rahmouni, Andréa Lessa Benedet, Annie Cohen, Oscar L. López, Thomas K. Karikari, Nicholas J. Ashton, Henrik Zetterberg, Kaj Blennow, Diogo O. Souza, Eduardo R. Zimmer, Pedro Rosa‐Neto, Tharick A. Pascoal

Bibliographic record

VenueAlzheimer s & Dementia · 2023
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsMontreal Neurological Institute and HospitalMcGill UniversityMcGill University Health Centre
Fundersnot available
KeywordsAstrocyteGlial fibrillary acidic proteinNeurograninBiomarkerNeuroscienceSynaptotagmin 1Synaptic plasticityPostsynaptic potentialMedicineInternal medicinePsychologyBiologyReceptorCentral nervous systemCell biologySynaptic vesicleBiochemistryImmunohistochemistrySignal transduction

Abstract

fetched live from OpenAlex

Abstract Background Biomarkers of astrocyte reactivity have the potential to improve diagnostic precision, disease monitoring, and treatment efficacy. Glial fibrillary acidic protein (GFAP) protein is expressed in astrocytes, which is important to synaptic plasticity, cell communication, and reactive gliosis. Method Cerebrospinal fluid (CSF) biomarkers were measured in participants of the McGill TRIAD cohort. 75 individuals (>50 years old, 44 cognitively unimpaired (CU), and 31 with cognitive impairment (CI)), had available Aß and tau‐PET. We measured CSF GFAP and synaptic markers (growth‐associated protein 43 (GAP‐43), neurogranin (Ng), synaptotagmin 1 (SYT1), presynaptic protein synaptosomal‐associated protein 25 (SNAP‐25)). Linear regressions adjusted for age, sex, clinical diagnosis, and Aß/tau‐PET were used to test the associations between astrocyte reactivity and synaptic function. Result Demographic information is shown in Table 1. We found an association between CSF GFAP and presynaptic markers (GAP‐43: p<0.0001, ß = 0.1076; SYT1: p<0.0001, ß = 0.0024; SNAP‐25 long: p<0.0001, ß = 0.0008) as well as postsynaptic markers (Ng: p<0.05, ß = 0.0066) independently of Aß and tau burden (Figure 1). Conclusion Our biomarker results support experimental literature suggesting that astrocyte reactivity plays a role in downstream synaptic dysfunction independent of the brain levels of Aß and tau tangles pathologies. This supports in vitro literature suggesting that therapeutic interventions targeting astrocyte reactivity can contribute to halting AD progression.

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)0.000
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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.035
GPT teacher head0.294
Teacher spread0.259 · 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

Citations0
Published2023
Admission routes2
Has abstractyes

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