Evidence map›Paper›PMID 35787714›Full record

ArticleJournal of neuroinflammation2022

Repopulated microglia induce expression of Cxcl13 with differential changes in Tau phosphorylation but do not impact amyloid pathology.

Berke Karaahmet, Linh Le, Monique S Mendes, Ania K Majewska, M Kerry O'Banion

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
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  11. Chronic palmitoylethanolamide administrationFrontiers in cellular neuroscience · 2025
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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

5 authors at 2 institutions in 1 country.

Berke Karaahmet *Department of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester School of Medicine & Dentistry, Rochester, NY, USA.ORCID http://orcid.org/0000-0003-2228-4967
Linh Le *Department of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester School of Medicine & Dentistry, Rochester, NY, USA.ORCID http://orcid.org/0000-0002-2762-7044
Monique S Mendes *Department of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester School of Medicine & Dentistry, Rochester, NY, USA.ORCID http://orcid.org/0000-0001-9800-5923
Ania K MajewskaDepartment of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester School of Medicine & Dentistry, Rochester, NY, USA. ania_majewska@urmc.rochester.edu.ORCID http://orcid.org/0000-0002-2167-6849
M Kerry O'BanionDepartment of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester School of Medicine & Dentistry, Rochester, NY, USA. Kerry_Obanion@urmc.rochester.edu.ORCID http://orcid.org/0000-0003-1246-3363
University of Rochester · USUniversity of Rochester Medical Center · US

Funding

VISUAL INDICES OF NEUROTOXICITYP30ES001247 · NIEHS · UNIVERSITY OF ROCHESTER · PI B Paige Lawrence · 1985 to 2026
$42.8M
Mechanism of IL-1 Dependent A-beta Plaque Clearance in Alzheimer's DiseaseR01AG030149 · NIA · UNIVERSITY OF ROCHESTER · PI O'BANION, M. KERRY · 2007 to 2018
$3.1M
Mechanisms that regulate microglial dynamics in the context of plasticity (Supplement)R01NS114480 · NINDS · UNIVERSITY OF ROCHESTER · PI MAJEWSKA, ANNA K · 2020 to 2024
$2.2M
The Role of Purinergic Signaling in Microglia Birth and Maturation in the Adult BrainK00NS108486 · NINDS · STANFORD UNIVERSITY · PI MENDES, MONIQUE SHANICE · 2021 to 2023
$232k
The role of purinergic signaling in mediating the dynamics of microglia repopulation following depletion in the adult cortex in vivoF99NS108486 · NINDS · UNIVERSITY OF ROCHESTER · PI MENDES, MONIQUE SHANICE · 2018 to 2020
$100k
Alzheimer's Association AARG-NTF-19-619116NIEHS NIH HHS P30 ES001247NIH HHS R01 AG030149NIH HHS R01 NS114480-2W2NINDS NIH HHS F99 NS108486NINDS NIH HHS K00 NS108486NINDS NIH HHS R01 NS114480
6 · The paper itself

Abstract

backgroundAdult microglia rely on self-renewal through division to repopulate and sustain their numbers. However, with aging, microglia display morphological and transcriptional changes that reflect a heightened state of neuroinflammation. This state threatens aging neurons and other cells and can influence the progression of Alzheimer's disease (AD). In this study, we sought to determine whether renewing microglia through a forced partial depletion/repopulation method could attenuate AD pathology in the 3xTg and APP/PS1 mouse models.

methodsWe pharmacologically depleted the microglia of two cohorts of 21- to 22-month-old 3xTg mice and one cohort of 14-month-old APP/PS1 mice using PLX5622 formulated in chow for 2 weeks. Following depletion, we returned the mice to standard chow diet for 1 month to allow microglial repopulation. We assessed the effect of depletion and repopulation on AD pathology, microglial gene expression, and surface levels of homeostatic markers on microglia using immunohistochemistry, single-cell RNAseq and flow cytometry.

resultsAlthough we did not identify a significant impact of microglial repopulation on amyloid pathology in either of the AD models, we observed differential changes in phosphorylated-Tau epitopes after repopulation in the 3xTg mice. We provide evidence that repopulated microglia in the hippocampal formation exhibited changes in the levels of homeostatic microglial markers. Lastly, we identified novel subpopulations of microglia by performing single-cell RNAseq analysis on CD45

conclusionOverall, we found that depleting and repopulating microglia causes overexpression of microglial Cxcl13 with disparate effects on Tau and amyloid pathologies.

Indexed as

Alzheimer DiseaseMicrogliaAmyloidogenic ProteinsAnimalsChemokine CXCL13HumansMiceMice, TransgenicPhosphorylationPlaque, Amyloidtau ProteinsAmyloidogenic ProteinsChemokine CXCL13CXCL13 protein, humanCxcl13 protein, mouseMapt protein, mousetau ProteinsAlzheimer’s diseaseColony-stimulating factor 1MicrogliaPLX5622RNAseq

Identifiers

PMID35787714
PMCPMC9252071
OpenAlexW4283795990

What OpenQuestion holds

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LicenceCC BY
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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.