Evidence map›Paper›PMID 41822299›Full record

SynthesisFrontiers in aging neuroscience2026

The impact of CSF1R inhibitor-mediated microglial depletion in rodent models of Alzheimer's and Parkinson's disease: a systematic review and meta-analysis.

Ana Flavia F Ferreira, Ana Caroline Santos-Silva, Beatriz Gangale Muratori, Luiz Roberto Britto

Abstract readSystematic Review
In one paragraph

Synthesis in Frontiers in aging neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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

4 authors.

Ana Flavia F FerreiraDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Ana Caroline Santos-SilvaDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Beatriz Gangale MuratoriDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Luiz Roberto BrittoDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Microglia are central nervous system immune cells that support brain homeostasis but can adopt harmful roles in neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), depending on the disease stage and progression. Thus, targeting microglia through depletion has emerged as a potential therapeutic approach. This systematic review and meta-analysis aim to evaluate the effects of microglial depletion using colony-stimulating factor 1 receptor (CSF1R) inhibitors, such as PLX3397 and PLX5622, in preclinical models of AD and PD. Twenty-six AD and seventeen PD preclinical studies were selected. In PD models, most studies reported neuroprotective effects after microglial depletion, though a few showed detrimental outcomes, particularly with shorter depletion protocols. Notably, almost all studies induced microglial depletion prior to or during disease onset, underscoring a major research gap. Behavioral results were contradictory, as some reported beneficial effects while others showed no effect or worsened behavior. In AD models, results were more variable, but many studies observed reduced neuroinflammation, improved cognition, and decreased amyloid-beta and tau pathology. Meta-analyses showed no overall reduction in dopaminergic neuron loss in PD or amyloid-beta levels in AD, though longer depletion protocols showed more favorable trends in both diseases. Despite the few reports, repopulation following microglial depletion may constitute a promising approach. Microglial depletion, via PLX3397 and PLX5622, may offer therapeutic potential for both AD and PD, although high heterogeneity and variability among studies are a clear limitation. Further studies are needed, particularly those assessing post-onset intervention, sex-specific effects, and broader behavioral and pathological endpoints to better understand the therapeutic potential of microglial modulation. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251075163.

Indexed as

CSF1-R inhibitionmicroglial depletionmicroglial repopulationneurodegenerationneuroprotection

Identifiers

PMID41822299
PMCPMC12975910

What Socratic 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 Socratic graph.