Evidence map›Paper›PMID 42399983›Full record

ArticleJournal of neuroinflammation2026

Regional mapping of CSF1R-positive microglia in neurodegenerative diseases and progressive MS, with exploratory presynaptic marker analyses.

Mahsa S Bavarsad, Felipe L Pereira, Marina M Reinhardt, Abhijit Satpati, Salvatore Spina, William W Seeley, William Jagust, Gil D Rabinovici, Ari Green, Lea T Grinberg

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Mahsa S BavarsadMemory and Aging Center, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
Felipe L PereiraMemory and Aging Center, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
Marina M ReinhardtDepartments of Laboratory Medicine and Pathology and Neurosciences, Mayo Clinic Florida, 4500 San Pablo Rd, Jacksonville, FL, 32250, USA.
Abhijit SatpatiMemory and Aging Center, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
Salvatore SpinaMemory and Aging Center, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
William W SeeleyMemory and Aging Center, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
William JagustHelen Wills Neuroscience Institute, University of California, Berkeley, CA, USA.
Gil D RabinoviciMemory and Aging Center, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
Ari GreenDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Lea T GrinbergMemory and Aging Center, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA. Grinberg.lea@mayo.edu.ORCID https://orcid.org/0000-0002-6809-0618

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMicroglial colony-stimulating factor-1 receptor (CSF1R) is a therapeutic and imaging target, yet the regional, disease-specific distribution of CSF1R-positive microglia in the human brain remains incompletely defined, limiting interpretation of emerging CSF1R-PET signals. We sought to build a cross-disease, multi-region, quantitative map of CSF1R-positive microglia in neurodegenerative conditions and progressive multiple sclerosis (MS) lesions, with an exploratory comparison to presynaptic marker burden.

methodsCSF1R mRNA‑positive microglia were quantified by RNAscope across six cortical regions (MFG, IFG, ITG, AG, CA1, EC) in early‑onset Alzheimer's disease (EOAD), late‑onset AD (LOAD), progressive supranuclear palsy (PSP), and frontotemporal lobar degeneration with TDP-43 inclusions due to progranulin mutation (FTLD‑GRN), and in primary and secondary progressive MS (PPMS, SPMS) within cortical gray‑matter plaques, plaque-adjacent gray matter and white matter. Positivity was defined a priori as ≥ 3 puncta with housekeeping‑probe pass and negative‑control verification, counting blinded, and densities were cortical‑thickness corrected. Iba-1 immunolabeling verified microglial identity. Western blot provided protein‑level verification. We explored ROI‑level associations of CSF1R with SV2A and synaptophysin previously measured in the same regions/cases.

resultsIn neurodegeneration, increases were smaller and region‑specific (e.g., EOAD-ITG/CA1; LOAD-AG; PSP-AG; FTLD‑GRN-IFG/ITG/AG/EC), with minimal white‑matter change. In progressive MS, gray-matter CSF1R-positive microglia densities did not differ from controls, whereas SPMS white matter was increased. Exploratory analysis showed that CSF1R and SV2A were positively associated across ROIs in neurodegenerative diseases (e.g., PSP approximately ρ = 0.66), and weakest in LOAD; synaptophysin showed similar patterns, suggesting that regions with higher CSF1R-positive microglia density can coincide with relative preservation of presynaptic markers.

conclusionsA cross‑disease, region‑resolved map reveals region‑specific changes in CSF1R + cell density in neurodegeneration, but only white matter in MS. These findings provide the histological context needed to interpret future CSF1R‑PET. Prospective studies pairing CSF1R‑PET with SV2A‑PET and multiplex tissue profiling are warranted to define microglial states and synaptic outcomes in vivo.

Indexed as

Brain MappingMicrogliaMultiple Sclerosis, Chronic ProgressiveNeurodegenerative DiseasesPresynaptic TerminalsReceptors, Granulocyte-Macrophage Colony-Stimulating FactorAgedAged, 80 and overBiomarkersFemaleHumansMaleMiddle AgedReceptor, Macrophage Colony-Stimulating FactorBiomarkersCSF1R protein, humanReceptor, Macrophage Colony-Stimulating FactorReceptors, Granulocyte-Macrophage Colony-Stimulating FactorAlzheimer’s DiseaseCSF1RFrontotemporal DementiaMicrogliaMultiple SclerosisSynapse/synaptic

Identifiers

PMID42399983
PMCPMC13602470

What OpenQuestion holds

Textmetadata
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.