Evidence map›Paper›PMID 35461266›Full record

ArticleAlzheimer's research & therapy2022

Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer's disease.

Pia Kivisäkk, Becky C Carlyle, Thadryan Sweeney, James P Quinn, Christopher E Ramirez, Bianca A Trombetta, Muriel Mendes, Mary Brock, Carrie Rubel, Julie Czerkowicz and 2 more

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

Article in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
10.8field-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

47 citing papers in PubMed, 95 citations in OpenAlex.

  1. Trial
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  3. Relationships of CSF biomarkers to cortical atrophy in early-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  10. The roles of biomarkers in Alzheimer's disease clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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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

12 authors at 3 institutions in 1 country.

Pia KivisäkkDepartment of Neurology, Alzheimer's Clinical and Translational Research Unit, Massachusetts General Hospital, 114 16th Street, Room 2300, Charlestown, MA, 02129, USA. pkivisakk@mgh.harvard.edu.
Becky C CarlyleDepartment of Neurology, Alzheimer's Clinical and Translational Research Unit, Massachusetts General Hospital, 114 16th Street, Room 2300, Charlestown, MA, 02129, USA.
Thadryan SweeneyDepartment of Neurology, Alzheimer's Clinical and Translational Research Unit, Massachusetts General Hospital, 114 16th Street, Room 2300, Charlestown, MA, 02129, USA.
James P QuinnDepartment of Neurology, Alzheimer's Clinical and Translational Research Unit, Massachusetts General Hospital, 114 16th Street, Room 2300, Charlestown, MA, 02129, USA.
Christopher E RamirezDepartment of Neurology, Alzheimer's Clinical and Translational Research Unit, Massachusetts General Hospital, 114 16th Street, Room 2300, Charlestown, MA, 02129, USA.
Bianca A TrombettaDepartment of Neurology, Alzheimer's Clinical and Translational Research Unit, Massachusetts General Hospital, 114 16th Street, Room 2300, Charlestown, MA, 02129, USA.
Muriel MendesQuanterix Corporation, Billerica, MA, USA.
Mary BrockQuanterix Corporation, Billerica, MA, USA.
Carrie RubelBiogen, Cambridge, MA, USA.
Julie CzerkowiczBiogen, Cambridge, MA, USA.
Danielle GrahamBiogen, Cambridge, MA, USA.
Steven E ArnoldDepartment of Neurology, Alzheimer's Clinical and Translational Research Unit, Massachusetts General Hospital, 114 16th Street, Room 2300, Charlestown, MA, 02129, USA.
Massachusetts General Hospital · USBiogen (United States) · USQuanterix (United States) · US

Funding

Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI STEVEN E ARNOLD · 2019 to 2026
$36.5M
CMP3: A CSF Multiple Pathophysiology Panel for Clinical Trials in Alzheimer's DiseaseRF1AG059856 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI ARNOLD, STEVEN E · 2018 to 2018
$1.3M
NIA NIH HHS P30 AG062421NIA NIH HHS RF1 AG059856
6 · The paper itself

Abstract

backgroundThere is currently a lack of reliable and easily accessible biomarkers predicting cognitive decline in Alzheimer's disease (AD). Synaptic dysfunction and loss occur early in AD and synaptic loss measured in the brain tissue and by PET are closely linked to cognitive decline, rendering synaptic proteins a promising target for biomarker development.

methodsWe used novel Simoa assays to measure cerebrospinal fluid (CSF) levels of two synaptic biomarker candidates, postsynaptic density protein 95 (PSD-95/DLG4), and the presynaptically localized synaptosomal-associated protein 25 (SNAP-25), as well as neurogranin (Ng), an established postsynaptic biomarker. CSF samples from two well-characterized cohorts (n=178 and n=156) were selected from banked samples obtained from diagnostic lumbar punctures containing subjects with amyloid-ß (Aß) positive AD, subjects with non-AD neurodegenerative diseases, subjects with other neurological conditions, and healthy controls (HC).

resultsAll subjects had detectable CSF levels of PSD-95, SNAP-25, and Ng. CSF levels of PSD-95, SNAP-25, and Ng were all correlated, with the strongest correlation between the presynaptic SNAP-25 and the postsynaptic neurogranin. AD subjects had on average higher concentrations of all three synaptic markers compared to those with non-AD neurodegenerative diseases, other neurological disorders, and HCs. Increased CSF levels of PSD-95, SNAP-25, and Ng were, however, not specific for AD and were present in sporadic cases with inflammatory or vascular disorders as well. High CSF levels of PSD-95 were also observed in a few subjects with other neurodegenerative disorders.

conclusionThe data establishes PSD-95 as a promising CSF marker for neurodegenerative disease synaptic pathology, while SNAP-25 and Ng appear to be somewhat more specific for AD. Together, these synaptic markers hold promise to identify early AD pathology, to correlate with cognitive decline, and to monitor responses to disease-modifying drugs reducing synaptic degeneration.

Indexed as

Alzheimer DiseaseCognitive DysfunctionNeurodegenerative DiseasesAmyloid beta-PeptidesBiomarkersDisks Large Homolog 4 ProteinHumansNeurograninSynaptosomal-Associated Protein 25tau ProteinsAmyloid beta-PeptidesBiomarkersDisks Large Homolog 4 ProteinNeurograninSynaptosomal-Associated Protein 25tau ProteinsAlzheimer’s diseaseBiomarkersCerebrospinal fluidNeurodegenerative diseasesNeurograninPSD-95SNAP-25Synaptic markers

Identifiers

PMID35461266
PMCPMC9034610
OpenAlexW4226497637

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.