Evidence map›Paper›PMID 30413160›Full record

ArticleJournal of neuroinflammation2018

Partial reduction of microglia does not affect tau pathology in aged mice.

Rachel E Bennett, Annie Bryant, Miwei Hu, Ashley B Robbins, Sarah C Hopp, Bradley T Hyman

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

Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 2 pooled it
4.3field-weighted citation impact, top 5% 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

42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

6 authors at 2 institutions in 1 country.

Rachel E BennettDepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Annie BryantDepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Miwei HuDepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Ashley B RobbinsDepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Sarah C HoppBiggs Institute for Alzheimer's and Neurodegenerative Disease, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA. hopps1@uthscsa.edu.ORCID http://orcid.org/0000-0001-5228-0022
Bradley T HymanDepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Harvard University · USThe University of Texas Health Science Center at San Antonio · US

Funding

THE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1M
Training in the Molecular Biology of Neurodegeneration and Alzheimer's DiseaseT32AG000222 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Bruce A YANKNER · 1992 to 2026
$18.5M
Are multiple tau species toxic in Alzheimer's Disease?RF1AG059789 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 2018 to 2018
$2.7M
National Institute on Aging AG005134National Institute on Aging AG059789-01NIA NIH HHS P50 AG005134NIA NIH HHS RF1 AG059789NIA NIH HHS T32 AG000222
6 · The paper itself

Abstract

backgroundActivation of inflammation pathways in the brain occurs in Alzheimer's disease and may contribute to the accumulation and spread of pathological proteins including tau. The goal of this study was to identify how changes in microglia, a key inflammatory cell type, may contribute to tau protein accumulation and pathology-associated changes in immune and non-immune cell processes such as neuronal degeneration, astrocyte physiology, cytokine expression, and blood vessel morphology.

methodsWe used PLX3397 (290 mg/kg), a colony-stimulating factor receptor 1 (CSF1R) inhibitor, to reduce the number of microglia in the brains of a tau-overexpressing mouse model. Mice were fed PLX3397 in chow or a control diet for 3 months beginning at 12 months of age and then were subsequently analyzed for changes in blood vessel morphology by in vivo two-photon microscopy and tissues were collected for biochemistry and histology.

resultsPLX3397 reduced microglial numbers by 30% regardless of genotype compared to control diet-treated mice. No change in tau burden, cortical atrophy, blood vessels, or astrocyte activation was detected. All Tg4510 mice were observed to have an increased in "disease-associated" microglial gene expression, but PLX3397 treatment did not reduce expression of these genes. Surprisingly, PLX3397 treatment resulted in upregulation of CD68 and Tgf1β.

conclusionsManipulating microglial activity may not be an effective strategy to combat tau pathological lesions. Higher doses of PLX3397 may be required or earlier intervention in the disease course. Overall, this indicates a need for a better understanding of specific microglial changes and their relation to the disease process.

Indexed as

AgingAminopyridinesAnimalsBlood VesselsCalcium-Binding ProteinsCalcium-Calmodulin-Dependent Protein Kinase Type 2CytokinesDisease Models, AnimalGene Expression RegulationMaleMiceMice, Inbred C57BLMice, TransgenicMicrofilament ProteinsMicrogliaMutationAif1 protein, mouseAminopyridinesCalcium-Binding ProteinsCalcium-Calmodulin-Dependent Protein Kinase Type 2Camk2a protein, mouseCsf1r protein, mouseCytokinesMapt protein, mouseMicrofilament ProteinspexidartinibPyrrolesReceptors, Granulocyte-Macrophage Colony-Stimulating FactorRNA, Messengertau ProteinsAlzheimer’s diseaseMicrogliaTau

Identifiers

PMID30413160
PMCPMC6230271
OpenAlexW2900345046

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.