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Record W4408105335 · doi:10.1186/s13195-025-01703-z

Synaptic protein CSF levels relate to memory scores in individuals without dementia

2025· article· en· W4408105335 on OpenAlexfundno aff
Kirsten E. J. Wesenhagen, Diederick Martijn de Leeuw, Jori Tomassen, Johan Gobom, Isabelle Bos, Stephanie J. B. Vos, Pablo Martínez‐Lage, Mikel Tainta, Julius Popp, Gwendoline Peyratout, Magda Tsolaki, Rik Vandenberghe, Yvonne Freund‐Levi, Frans Verhey, Simon Lovestone, Johannes Streffer, Valerija Dobričić, Kaj Blennow, Philip Scheltens, August B. Smit, Lars Bertram, Charlotte E. Teunissen, Henrik Zetterberg, Betty M. Tijms, Pieter Jelle Visser

Bibliographic record

VenueAlzheimer s Research & Therapy · 2025
Typearticle
Languageen
FieldMedicine
TopicDementia and Cognitive Impairment Research
Canadian institutionsnot available
FundersNational Institute on AgingCanadian Institutes of Health ResearchGenentechNational Institutes of HealthUK Dementia Research InstituteIXICOH. Lundbeck A/SServierInnovative Medicines InitiativeAlzheimer's Drug Discovery FoundationZonMwAlzheimerfondenEuropean CommissionFamiljen Erling-Perssons StiftelseHjärnfondenVetenskapsrådetEisaiEU Joint Programme – Neurodegenerative Disease ResearchEuropean Research CouncilNorthern California Institute for Research and EducationPfizerBiogenBioClinicaUniversity of Southern CaliforniaAlzheimer's AssociationStiftelsen för Gamla TjänarinnorEli Lilly and CompanyU.S. Department of DefenseDemensfondenMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeDemensförbundetNovartis Pharmaceuticals CorporationBristol-Myers Squibb
KeywordsBiomarkerDementiaNeuroscienceNeurologyNeuroimagingRecallAmyloid (mycology)CognitionDiseaseMedicinePsychologyOncologyInternal medicinePathologyBiologyBiochemistryCognitive psychology

Abstract

fetched live from OpenAlex

BACKGROUND: We investigated how cerebrospinal fluid levels of synaptic proteins associate with memory function in normal cognition (CN) and mild cognitive impairment (MCI), and investigated the effect of amyloid positivity on these associations. METHODS: We included 242 CN (105(43%) abnormal amyloid), and 278 MCI individuals (183(66%) abnormal amyloid) from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). For 181 (EMIF-AD MBD) and 36 (ADNI) proteins with a synaptic annotation in SynGO, associations with word learning recall were analysed with linear models. RESULTS: Subsets of synaptic proteins showed lower levels with worse recall in preclinical AD (EMIF-AD MBD: 7, ADNI: 5 proteins, none overlapping), prodromal AD (EMIF-AD MBD only, 27 proteins) and non-AD MCI (EMIF-AD MBD: 1, ADNI: 7 proteins). The majority of these associations were specific to these clinical groups. CONCLUSIONS: Synaptic disturbance-related memory impairment occurred very early in AD, indicating it may be relevant to develop therapies targeting the synapse early in the disease.

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)0.003
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 score0.003
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
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 integrity0.0010.000
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 head0.100
GPT teacher head0.422
Teacher spread0.323 · 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

Citations4
Published2025
Admission routes1
Has abstractyes

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