Evidence map›Paper›PMID 36964594›Full record

ArticleAlzheimer's research & therapy2023

Synaptic biomarkers in the cerebrospinal fluid associate differentially with classical neuronal biomarkers in patients with Alzheimer's disease and frontotemporal dementia.

Shreyasee Das, Julie Goossens, Dirk Jacobs, Nele Dewit, Yolande A L Pijnenburg, Sjors G J G In 't Veld, Charlotte E Teunissen, Eugeen Vanmechelen

Open access · goldFull text read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
10.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

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  11. Prediction of longitudinal synaptic loss in Alzheimer's disease using tau PET and plasma biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Shreyasee DasADxNeuroSciences NV, Zwijnaarde 94, 9052, Ghent, Belgium.
Julie GoossensADxNeuroSciences NV, Zwijnaarde 94, 9052, Ghent, Belgium.
Dirk JacobsADxNeuroSciences NV, Zwijnaarde 94, 9052, Ghent, Belgium.
Nele DewitMedpace, Technologielaan 11, 3001, Leuven, Belgium.
Yolande A L PijnenburgNeurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Program Neurodegeneration, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Sjors G J G In 't VeldNeurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Program Neurodegeneration, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Charlotte E TeunissenNeurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Program Neurodegeneration, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Eugeen VanmechelenADxNeuroSciences NV, Zwijnaarde 94, 9052, Ghent, Belgium. eugeen.vanmechelen@adxneurosciences.com.
Vrije Universiteit Amsterdam · NLAblynx (Belgium) · BEAmsterdam Neuroscience · NLAmsterdam University Medical Centers · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLoss of synaptic functionality has been recently identified as an early-stage indicator of neurological diseases. Consequently, monitoring changes in synaptic protein levels may be relevant for observing disease evolution or treatment responses in patients. Here, we have studied the relationship between fluid biomarkers of neurodegeneration and synaptic dysfunction in patients with Alzheimer's disease (AD), frontotemporal dementia (FTD), and subjective cognitive decline (SCD).

methodsThe exploratory cohort consisted of cerebrospinal fluid (CSF) samples (n = 60) from patients diagnosed with AD (n = 20), FTD (n = 20), and SCD (n = 20) from the Amsterdam Dementia Cohort. We developed two novel immunoassays for the synaptic proteins synaptosomal-associated protein-25 (SNAP25) and vesicle-associated membrane protein-2 (VAMP2). We measured the levels of these biomarkers in CSF, in addition to neuronal pentraxin-2 (NPTX2), glutamate ionotropic receptor-4 (GluR4), and neurogranin (Ng) for this cohort. All in-house immunoassays were validated and analytically qualified prior to clinical application. CSF neurogranin (Ng) was measured using a commercially available ELISA.

resultsThis pilot study indicated that SNAP25, VAMP2, and Ng may not be specific biomarkers for AD as their levels were significantly elevated in patients with both AD and FTD compared to SCD. Moreover, the strength of the correlations between synaptic proteins was lower in the AD and FTD clinical groups compared to SCD. SNAP25, VAMP2, and Ng correlated strongly with each other as well as with total Tau (Tau) and phosphorylated Tau (PTau) in all three clinical groups. However, this correlation was weakened or absent with NPTX2 and GluR4. None of the synaptic proteins correlated to neurofilament light (NfL) in any clinical group.

conclusionThe correlation of the synaptic biomarkers with CSF Tau and PTau but the lack thereof with NfL implies that distinct pathological pathways may be involved in synaptic versus axonal degeneration. Our results reflect the diversity of synaptic pathology in neurodegenerative dementias.

Indexed as

Alzheimer DiseaseCognitive DysfunctionFrontotemporal DementiaAmyloid beta-PeptidesBiomarkersHumansNeurograninPilot Projectstau ProteinsVesicle-Associated Membrane Protein 2Amyloid beta-PeptidesBiomarkersNeurogranintau ProteinsVesicle-Associated Membrane Protein 2Alzheimer’s diseaseBiomarkersDementiaFrontotemporal dementiaImmunoassaySynapse

Identifiers

PMID36964594
PMCPMC10037899
OpenAlexW4360863494

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read58
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.