Evidence map›Paper›PMID 29435980›Full record

ArticleThe Journal of pathology2018

The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer's disease.

Andre F Batista, Leticia Forny-Germano, Julia R Clarke, Natalia M Lyra E Silva, Jordano Brito-Moreira, Susan E Boehnke, Andrew Winterborn, Brian C Coe, Ann Lablans, Juliana F Vital and 9 more

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

Article in The Journal of pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed, 5 pooled it
16.3field-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

141 citing papers in PubMed, 5 syntheses or guidelines pooled it, 238 citations in OpenAlex.

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  15. The landscape of dementia research, diagnosis, treatment, and care in Latin America.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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81 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

19 authors at 6 institutions in 4 countries.

Andre F BatistaInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Leticia Forny-GermanoInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Julia R ClarkeSchool of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Natalia M Lyra E SilvaInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Jordano Brito-MoreiraInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Susan E BoehnkeCentre for Neuroscience Studies, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Andrew WinterbornAnimal Care Service, Queen's University, Kingston, Ontario, Canada.
Brian C CoeCentre for Neuroscience Studies, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Ann LablansCentre for Neuroscience Studies, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Juliana F VitalInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Suelen A MarquesDepartament of Neurobiology, Fluminense Federal University, Niteroi, Brazil.
Ana Mb MartinezDepartment of Pathology, Faculty of Medicine, Hospital Universitário Clementino Fraga Filho, UFRJ, Rio de Janeiro, Brazil.
Matthias GralleInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Christian HolscherDivision of Biomed and Life Sciences, Faculty of Health and Medicine Lancaster University, Lancaster, UK.
William L KleinDepartment of Neurobiology, Northwestern University, Evanston, Illinois, USA.
Jean-Christophe HouzelInstitute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Sergio T FerreiraInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Douglas P MunozCentre for Neuroscience Studies, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Fernanda G De FeliceInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.ORCID 0000-0001-8358-0589
Universidade Federal do Rio de Janeiro · BRQueen's University · CAHospital Universitário Clementino Fraga Filho · BRLancaster University · GBNorthwestern University · USUniversidade Federal Fluminense · BR

Funding

CIHR
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling. Here, we show that liraglutide prevented the loss of brain insulin receptors and synapses, and reversed memory impairment induced by AD-linked amyloid-β oligomers (AβOs) in mice. Using hippocampal neuronal cultures, we determined that the mechanism of neuroprotection by liraglutide involves activation of the PKA signaling pathway. Infusion of AβOs into the lateral cerebral ventricle of non-human primates (NHPs) led to marked loss of insulin receptors and synapses in brain regions related to memory. Systemic treatment of NHPs with liraglutide provided partial protection, decreasing AD-related insulin receptor, synaptic, and tau pathology in specific brain regions. Synapse damage and elimination are amongst the earliest known pathological changes and the best correlates of memory impairment in AD. The results illuminate mechanisms of neuroprotection by liraglutide, and indicate that GLP-1 receptor activation may be harnessed to protect brain insulin receptors and synapses in AD. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsCognitive DysfunctionDisease Models, AnimalHippocampusHypoglycemic AgentsLiraglutideMaleMemoryMiceReceptor, InsulinSynapsesAmyloid beta-PeptidesHypoglycemic AgentsLiraglutideReceptor, InsulinAlzheimer's diseasediabetesGLP-1insulin receptorsliraglutideneurodegenerationnon-human primatesPKA signalingsynapse damagetau pathology

Identifiers

PMID29435980
PMCPMC5947670
OpenAlexW2793413710

What OpenQuestion holds

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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.