Evidence map›Paper›PMID 26555315›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2016

Corticotropin-releasing factor receptor-1 antagonism mitigates beta amyloid pathology and cognitive and synaptic deficits in a mouse model of Alzheimer's disease.

Cheng Zhang, Ching-Chang Kuo, Setareh H Moghadam, Louise Monte, Shannon N Campbell, Kenner C Rice, Paul E Sawchenko, Eliezer Masliah, Robert A Rissman

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

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
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  8. Experimental laboratory models as tools for understanding modifiable dementia risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
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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

9 authors at 4 institutions in 1 country.

Cheng ZhangDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Ching-Chang KuoNeuroInformatics Center, University of Oregon, Eugene, OR, USA.
Setareh H MoghadamDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Louise MonteDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Shannon N CampbellDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Kenner C RiceChemical Biology Research Branch, National Institute on Drug Abuse and Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Paul E SawchenkoSalk Institute for Biological Studies, La Jolla, CA, USA.
Eliezer MasliahDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA; Department of Pathology, University of California San Diego, La Jolla, CA, USA.
Robert A RissmanDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA. Electronic address: rrissman@ucsd.edu.
University of California, San Diego · USNational Institute on Alcohol Abuse and Alcoholism · USSalk Institute for Biological Studies · USUniversity of Oregon · US

Funding

TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
RECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6M
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
TARGETED DISRUPTION OF NEUROENDOCRINE GENESP01DK026741 · NIDDK · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI ZORRILLA, ERIC P, ZORRILLA, ERIC P · 1986 to 2014
$31.6M
B-Synuclein as a Treatment for Lewy Body DiseaseR01AG018440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RISSMAN, ROBERT · 2001 to 2021
$5.2M
Stress and CRF Signaling in Alzheimer?s Disease PathogenesisR01AG032755 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI RISSMAN, ROBERT, SAWCHENKO, PAUL E. · 2008 to 2012
$1.9M
Medicinal Chemistry of Drugs Acting on CRH ReceptorsZIADA000528 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI RICE, KENNER · 2009 to 2018
$1.8M
Polytherapy for AD: Combining Gamma-secretase Modulation and CRFR1 AntagonismR21AG047484 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RISSMAN, ROBERT, WAGNER, STEVEN LEE · 2014 to 2015
$419k
NIA NIH HHS P50 AG005131NIA NIH HHS R01 AG018440NIA NIH HHS R01 AG032755NIA NIH HHS R21 AG047484NIA NIH HHS U01 AG010483NIA NIH HHS U19 AG010483NIDDK NIH HHS P01 DK026741
6 · The paper itself

Abstract

introductionStress and corticotropin-releasing factor (CRF) have been implicated as mechanistically involved in Alzheimer's disease (AD), but agents that impact CRF signaling have not been carefully tested for therapeutic efficacy or long-term safety in animal models.

methodsTo test whether antagonism of the type-1 corticotropin-releasing factor receptor (CRFR1) could be used as a disease-modifying treatment for AD, we used a preclinical prevention paradigm and treated 30-day-old AD transgenic mice with the small-molecule, CRFR1-selective antagonist, R121919, for 5 months, and examined AD pathologic and behavioral end points.

resultsR121919 significantly prevented the onset of cognitive impairment in female mice and reduced cellular and synaptic deficits and beta amyloid and C-terminal fragment-β levels in both genders. We observed no tolerability or toxicity issues in mice treated with R121919. DISCUSSION: CRFR1 antagonism presents a viable disease-modifying therapy for AD, recommending its advancement to early-phase human safety trials.

Indexed as

Disease Models, AnimalReceptors, Corticotropin-Releasing HormoneAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBrainCognitionCRF Receptor, Type 1HumansMiceMice, TransgenicPyrimidinesSynapsesAmyloid beta-PeptidesAmyloid beta-Protein PrecursorCRF Receptor, Type 1PyrimidinesR 121919Receptors, Corticotropin-Releasing HormoneAlzheimer's diseaseBeta amyloidCognitive deficitsCorticotropin-releasing factor receptorCorticotropin-releasing hormoneHippocampusR121919StressSynaptic deficits

Identifiers

PMID26555315
PMCPMC4860182
OpenAlexW2173193555

What OpenQuestion holds

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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.