Evidence map›Paper›PMID 29700597›Full record

ArticleActa neuropathologica2018

Cerebrospinal fluid neurogranin concentration in neurodegeneration: relation to clinical phenotypes and neuropathology.

Erik Portelius, Bob Olsson, Kina Höglund, Nicholas C Cullen, Hlin Kvartsberg, Ulf Andreasson, Henrik Zetterberg, Åsa Sandelius, Leslie M Shaw, Virginia M Y Lee and 11 more

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

Article in Acta neuropathologica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 3 pooled it
13.1field-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

95 citing papers in PubMed, 3 syntheses or guidelines pooled it, 175 citations in OpenAlex.

  1. Pooled it
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  7. Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021
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  19. New Research on Biomarkers in Alzheimer's Continuum.Reviews on recent clinical trials · 2025
    Review
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35 more citing papers are in PubMed but not listed here.

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

21 authors at 7 institutions in 3 countries.

Erik PorteliusDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80, Mölndal, Sweden. erik.portelius@neuro.gu.se.ORCID 0000-0003-2708-7372
Bob OlssonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80, Mölndal, Sweden.
Kina HöglundDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80, Mölndal, Sweden.
Nicholas C CullenDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80, Mölndal, Sweden.
Hlin KvartsbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80, Mölndal, Sweden.
Ulf AndreassonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80, Mölndal, Sweden.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80, Mölndal, Sweden.
Åsa SandeliusDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80, Mölndal, Sweden.
Leslie M ShawDepartment of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Virginia M Y LeeDepartment of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
David J IrwinDepartment of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Murray GrossmanDepartment of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Daniel WeintraubDepartment of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Alice Chen-PlotkinDepartment of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
David A WolkDepartment of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Leo McCluskeyDepartment of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Lauren ElmanDepartment of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Jennifer McBrideDepartment of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Jon B ToledoDepartment of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
John Q TrojanowskiDepartment of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80, Mölndal, Sweden.
University of Pennsylvania · USSahlgrenska University Hospital · SEInstitute on Aging · USUniversity of Gothenburg · SEMental Illness Research, Education and Clinical Centers · USMethodist Hospital · USQueen Mary University of London · GB

Funding

Transgenic Mouse Models of Tau PathologiesP01AG017586 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LEE, VIRGINIA M · 2000 to 2021
$37.3M
UPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI XIE, SHARON XIANGWEN · 1991 to 2020
$35.1M
Project IV: "Alpha-Synuclein Strains & Diverse Synucleinopathies"P50NS053488 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI TROJANOWSKI, JOHN Q. · 2007 to 2017
$20.9M
Identification of Endophenotypes in the Behavioral-Variant of Frontotemporal DemeK23NS088341 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI IRWIN, DAVID JOHN · 2014 to 2018
$836k
Towards a blood-based diagnostic panel for confirmation of Parkinson's diseaseU01NS097056 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI CHEN-PLOTKIN, ALICE S · 2017 to 2019
$785k
NIA NIH HHS P01 AG017586NIA NIH HHS P30 AG010124NINDS NIH HHS K23 NS088341NINDS NIH HHS P50 NS053488NINDS NIH HHS U01 NS097056
6 · The paper itself

Abstract

Neurogranin (Ng) is a post-synaptic protein that previously has been shown to be a biomarker for synaptic function when measured in cerebrospinal fluid (CSF). The CSF concentration of Ng is increased in Alzheimer's disease dementia (ADD), and even in the pre-dementia stage. In this prospective study, we used an enzyme-linked immunosorbent assay that quantifies Ng in CSF to test the performance of Ng as a marker of synaptic function. In 915 patients, CSF Ng was evaluated across several different neurodegenerative diseases. Of these 915 patients, 116 had a neuropathologically confirmed definitive diagnosis and the relation between CSF Ng and topographical distribution of different pathologies in the brain was evaluated. CSF Ng was specifically increased in ADD compared to eight other neurodegenerative diseases, including Parkinson's disease (p < 0.0001), frontotemporal dementia (p < 0.0001), and amyotrophic lateral sclerosis (p = 0.0002). Similar results were obtained in neuropathologically confirmed cases. Using a biomarker index to evaluate whether CSF Ng contributed diagnostic information to the core AD CSF biomarkers (amyloid β (Aβ), t-tau, and p-tau), we show that Ng significantly increased the discrimination between AD and several other disorders. Higher CSF Ng levels were positively associated with greater Aβ neuritic plaque (Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuritic plaque score, p = 0.0002) and tau tangle pathology (Braak neurofibrillary tangles staging, p = 0.0007) scores. In the hippocampus and amygdala, two brain regions heavily affected in ADD with high expression of Ng, CSF Ng was associated with plaque (p = 0.0006 and p < 0.0001), but not with tangle, α-synuclein, or TAR DNA-binding protein 43 loads. These data support that CSF Ng is increased specifically in ADD, that high CSF Ng concentrations likely reflect synaptic dysfunction and that CSF Ng is associated with β-amyloid plaque pathology.

Indexed as

AgedAged, 80 and overalpha-SynucleinAmyloid beta-PeptidesFemaleHippocampusHumansMaleMiddle AgedNeurodegenerative DiseasesNeurofibrillary TanglesNeurograninPhenotypeProspective Studiestau Proteinsalpha-SynucleinAmyloid beta-PeptidesNeurogranintau ProteinsAlzheimer’s diseaseBiomarkerCerebrospinal fluidNeurograninNeuropathology

Identifiers

PMID29700597
PMCPMC6096740
OpenAlexW2800441976

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.