Evidence map›Paper›PMID 33353563›Full record

ArticleAlzheimer's research & therapy2020

Full-length and C-terminal neurogranin in Alzheimer's disease cerebrospinal fluid analyzed by novel ultrasensitive immunoassays.

Annika Öhrfelt, Julien Dumurgier, Henrik Zetterberg, Agathe Vrillon, Nicholas J Ashton, Hlin Kvartsberg, Elodie Bouaziz-Amar, Jacques Hugon, Claire Paquet, Kaj Blennow

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

Article in Alzheimer's research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 26% 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

8 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
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

10 authors at 3 institutions in 3 countries.

Annika ÖhrfeltDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital/Mölndal, SE-431 80, Mölndal, Sweden. annika.ohrfelt@neuro.gu.se.ORCID 0000-0001-8942-4181
Julien DumurgierUniversité de Paris, INSERM U1144, Center of Cognitive Neurology, Lariboisière - Fernand-Widal Hospital, APHP, Paris, France.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital/Mölndal, SE-431 80, Mölndal, Sweden.
Agathe VrillonUniversité de Paris, INSERM U1144, Center of Cognitive Neurology, Lariboisière - Fernand-Widal Hospital, APHP, Paris, France.
Nicholas J AshtonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital/Mölndal, SE-431 80, Mölndal, Sweden.
Hlin KvartsbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital/Mölndal, SE-431 80, Mölndal, Sweden.
Elodie Bouaziz-AmarDepartment of Biochemistry, Lariboisière - Fernand-Widal Hospital, Université de Paris, INSERMU1144, APHP, Paris, France.
Jacques HugonUniversité de Paris, INSERM U1144, Center of Cognitive Neurology, Lariboisière - Fernand-Widal Hospital, APHP, Paris, France.
Claire PaquetUniversité de Paris, INSERM U1144, Center of Cognitive Neurology, Lariboisière - Fernand-Widal Hospital, APHP, Paris, France.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital/Mölndal, SE-431 80, Mölndal, Sweden.
Inserm · FRSahlgrenska University Hospital · SEKing's College London · GB

Funding

European Research Council 681712
6 · The paper itself

Abstract

backgroundNeurogranin (Ng) is a neuron-specific and postsynaptic protein that is abundantly expressed in the brain, particularly in the dendritic spine of the hippocampus and cerebral cortex. The enzymatic cleavage of Ng produces fragments that are released into cerebrospinal (CSF), which have been shown to be elevated in Alzheimer's disease (AD) patients and predict cognitive decline. Thus, quantification of distinctive cleavage products of Ng could elucidate different features of the disease.

methodsIn this study, we developed novel ultrasensitive single molecule array (Simoa) assays for measurement of full-length neurogranin (FL-Ng) and C-terminal neurogranin (CT-Ng) fragments in CSF. The Ng Simoa assays were evaluated in CSF samples from AD patients (N = 23), mild cognitive impairment due to AD (MCI-AD) (N = 18), and from neurological controls (N = 26).

resultsThe intra-assay repeatability and inter-assay precision of the novel methods had coefficients of variation below 7% and 14%, respectively. CSF FL-Ng and CSF CT-Ng median concentrations were increased in AD patients (6.02 ng/L, P < 0.00001 and 452 ng/L, P = 0.00001, respectively) and in patients with MCI-AD (5.69 ng/L, P < 0.00001 and 566 ng/L, P < 0.00001) compared to neurological controls (0.644 ng/L and 145 ng/L). The median CSF ratio of CT-Ng/FL-Ng were decreased in AD patients (ratio = 101, P = 0.008) and in patients with MCI-AD (ratio = 115, P = 0.016) compared to neurological controls (ratio = 180). CSF of FL-Ng, CT-Ng, and ratio of CT-Ng/FL-Ng could each significantly differentiate AD patients from controls (FL-Ng, AUC = 0.907; CT-Ng, AUC = 0.913; CT-Ng/FL-Ng, AUC = 0.775) and patients with MCI-AD from controls (FL-Ng, AUC = 0.937; CT-Ng, AUC = 0.963; CT-Ng/FL-Ng, AUC = 0.785).

conclusionsAssessments of the FL-Ng and CT-Ng levels in CSF with the novel sensitive immunoassays provide a high separation of AD from controls, even in early phase of the disease. The novel Ng assays are robust and highly sensitive and may be valuable tools to study synaptic alteration in AD, as well as to monitor the effect on synaptic integrity of novel drug candidates in clinical trials.

Indexed as

Alzheimer DiseaseCognitive DysfunctionAmyloid beta-PeptidesBiomarkersHumansImmunoassayNeurograninPeptide Fragmentstau ProteinsAmyloid beta-PeptidesBiomarkersNeurograninPeptide Fragmentstau ProteinsAlzheimer’s diseaseBiomarkersCerebrospinal fluidMild cognitive impairmentNeurograninSingle molecule arraySNAP-25SynapticSynaptotagmin-1

Identifiers

PMID33353563
PMCPMC7756958
OpenAlexW3113770187

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.