Evidence map›Paper›PMID 29490706›Full record

ArticleMolecular neurodegeneration2018

Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer's disease.

Justyna Sosna, Stephan Philipp, Ricardo Albay, Jorge Mauricio Reyes-Ruiz, David Baglietto-Vargas, Frank M LaFerla, Charles G Glabe

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

Article in Molecular neurodegeneration, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 216 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
216citing papers in PubMed, 2 pooled it
20.6field-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

216 citing papers in PubMed, 2 syntheses or guidelines pooled it, 403 citations in OpenAlex.

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  7. Human IL-34 Deficiency Primes Microglia Toward Alzheimer's Disease-Associated States.medRxiv : the preprint server for health sciences · 2026
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156 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

7 authors at 2 institutions in 2 countries.

Justyna SosnaDepartment of Molecular Biology and Biochemistry, University of California, Irvine, USA.
Stephan PhilippDepartment of Molecular Biology and Biochemistry, University of California, Irvine, USA.
Ricardo AlbayDepartment of Molecular Biology and Biochemistry, University of California, Irvine, USA.
Jorge Mauricio Reyes-RuizDepartment of Molecular Biology and Biochemistry, University of California, Irvine, USA.
David Baglietto-VargasInstitute for Memory Impairments and Neurological Disorders (UCIMIND), University of California, Irvine, USA.
Frank M LaFerlaInstitute for Memory Impairments and Neurological Disorders (UCIMIND), University of California, Irvine, USA.
Charles G GlabeDepartment of Molecular Biology and Biochemistry, University of California, Irvine, USA. cglabe@uci.edu.
University of California, Irvine · USKing Abdulaziz University · SA

Funding

TISSUE REPOSITORY COREP01AG000538 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 1985 to 2018
$24.8M
Conformational polymorphisms of amyloid in AD and immunological biomarkers and therapeuticsRF1AG056507 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI GLABE, CHARLES G. · 2018 to 2019
$3.6M
Learning and Memory Impairments in Transgenic AD ModelsR01AG027544 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2007 to 2016
$3.1M
Conformational polymorphisms of amyloid in AD and immunological biomarkers and therapeuticsR56AG056507 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI GLABE, CHARLES G. · 2017 to 2017
$699k
Alzheimer's Association NIRG-15-363477NIA NIH HHS AG00538NIA NIH HHS AG027544NIA NIH HHS AG056507NIA NIH HHS P01 AG000538NIA NIH HHS R01 AG027544NIA NIH HHS R56 AG056507NIA NIH HHS RF1 AG056507
6 · The paper itself

Abstract

backgroundBesides the two main classical features of amyloid beta aggregation and tau-containing neurofibrillary tangle deposition, neuroinflammation plays an important yet unclear role in the pathophysiology of Alzheimer's disease (AD). Microglia are believed to be key mediators of neuroinflammation during AD and responsible for the regulation of brain homeostasis by balancing neurotoxicity and neuroprotective events. We have previously reported evidence that neuritic plaques are derived from dead neurons that have accumulated intraneuronal amyloid and further recruit Iba1-positive cells, which play a role in either neuronal demise or neuritic plaque maturation or both.

methodsTo study the impact of microglia on neuritic plaque development, we treated two-month-old 5XFAD mice with a selective colony stimulation factor 1 receptor (CSF1R) inhibitor, PLX3397, for a period of 3 months, resulting in a significant ablation of microglia. Directly after this treatment, we analyzed the amount of intraneuronal amyloid and neuritic plaques and performed behavioral studies including Y-maze, fear conditioning and elevated plus maze.

resultsWe found that early long-term PLX3397 administration results in a dramatic reduction of both intraneuronal amyloid as well as neuritic plaque deposition. PLX3397 treated young 5XFAD mice also displayed a significant decrease of soluble fibrillar amyloid oligomers in brain lysates, a depletion of soluble pre-fibrillar oligomers in plasma and an improvement in cognitive function measured by fear conditioning tests.

conclusionsOur findings demonstrate that CSF1R signaling, either directly on neurons or mediated by microglia, is crucial for the accumulation of intraneuronal amyloid and formation of neuritic plaques, suggesting that these two events are serially linked in a causal pathway leading to neurodegeneration and neuritic plaque formation. CSF1R inhibitors represent potential preventative or therapeutic approach that target the very earliest stages of the formation of intraneuronal amyloid and neuritic plaques.

Indexed as

Alzheimer DiseaseAminopyridinesAmyloidogenic ProteinsAnimalsBrainDisease Models, AnimalMiceMice, TransgenicMicrogliaNeuronsPlaque, AmyloidPyrrolesReceptors, Granulocyte-Macrophage Colony-Stimulating FactorAminopyridinesAmyloidogenic ProteinsCsf1r protein, mousepexidartinibPyrrolesReceptors, Granulocyte-Macrophage Colony-Stimulating FactorAlzheimer’s diseaseAmyloid betaIntraneuronal amyloidMicrogliaNeuroinflammationPlaques

Identifiers

PMID29490706
PMCPMC5831225
OpenAlexW2794408899

What OpenQuestion holds

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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.