Evidence map›Paper›PMID 39090679›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024

Primate cerebrospinal fluid CHI3L1 reflects brain TREM2 agonism.

Stephen P Schauer, Chang Hoon Cho, Gloriia Novikova, Gillie A Roth, Julie Lee, Anup D Sharma, Alejandro R Foley, Carl Ng, Philip Shen, Meena Choi and 37 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025
    Review
  4. Review
  5. Primate cerebrospinal fluid CHI3L1 reflects brain TREM2 agonism.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
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

47 authors.

Stephen P SchauerDepartment of Translational Medicine, Genentech, Inc., South San Francisco, California, USA.
Chang Hoon ChoDepartment of Human Pathobiology and OMNI Reverse Translation, Genentech, Inc., South San Francisco, California, USA.
Gloriia NovikovaDepartment of Bioinformatics, Genentech, Inc., South San Francisco, California, USA.
Gillie A RothDepartment of Preclinical and Translational Pharmacokinetics and Pharmacodynamics, Genentech, Inc., South San Francisco, California, USA.
Julie LeeDepartment of Translational Medicine, Genentech, Inc., South San Francisco, California, USA.
Anup D SharmaDepartment of Human Pathobiology and OMNI Reverse Translation, Genentech, Inc., South San Francisco, California, USA.
Alejandro R FoleyDepartment of BioAnalytical Sciences, Genentech, Inc., South San Francisco, California, USA.
Carl NgDepartment of BioAnalytical Sciences, Genentech, Inc., South San Francisco, California, USA.
Philip ShenDepartment of Safety Assessment Pathology, Genentech, Inc., South San Francisco, California, USA.
Meena ChoiDepartment of Microchemistry, Proteomics, Lipidomics, and Next Generation Sequencing, Genentech, Inc., South San Francisco, California, USA.
Taylur P MaDepartment of Microchemistry, Proteomics, Lipidomics, and Next Generation Sequencing, Genentech, Inc., South San Francisco, California, USA.
Lilian PhuDepartment of Microchemistry, Proteomics, Lipidomics, and Next Generation Sequencing, Genentech, Inc., South San Francisco, California, USA.
Hanna G BudayevaDepartment of Microchemistry, Proteomics, Lipidomics, and Next Generation Sequencing, Genentech, Inc., South San Francisco, California, USA.
Tommy K CheungDepartment of Microchemistry, Proteomics, Lipidomics, and Next Generation Sequencing, Genentech, Inc., South San Francisco, California, USA.
Guita LalehzadehDepartment of Neuroscience, Genentech, Inc., South San Francisco, California, USA.
Jose ImperioDepartment of Neuroscience, Genentech, Inc., South San Francisco, California, USA.
Hai NguDepartment of Research Pathology, Genentech, Inc., South San Francisco, California, USA.
Ainhoa EtxeberriaDepartment of Neuroscience, Genentech, Inc., South San Francisco, California, USA.
Yuxin LiangDepartment of Microchemistry, Proteomics, Lipidomics, and Next Generation Sequencing, Genentech, Inc., South San Francisco, California, USA.
Mitchell G RezzonicoDepartment of Bioinformatics, Genentech, Inc., South San Francisco, California, USA.
Michelle DouradoDepartment of Neuroscience, Genentech, Inc., South San Francisco, California, USA.
Kevin HuangDepartment of Translational Medicine, Genentech, Inc., South San Francisco, California, USA.
Zijuan LaiDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California, USA.
Martha HokomDepartment of BioAnalytical Sciences, Genentech, Inc., South San Francisco, California, USA.
Nikhil J PandyaDepartment of Human Pathobiology and OMNI Reverse Translation, Genentech, Inc., South San Francisco, California, USA.
Dwight NewtonRoche Informatics, Hoffmann-La Roche, Ltd., Mississauga, Ontario, Canada.
Alyaa M Abdel-HaleemRoche Informatics, Hoffmann-La Roche, Ltd., Mississauga, Ontario, Canada.
Pamela ChanDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, California, USA.
Donna LeeDepartment of Safety Assessment Toxicology, Genentech, Inc., South San Francisco, California, USA.
Nardos G TassewDepartment of Safety Assessment Toxicology, Genentech, Inc., South San Francisco, California, USA.
Dewakar SangarajuDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California, USA.
Deborah O'ConnorDepartment of Chemistry, Manufacturing, and Controls, Genentech, Inc., South San Francisco, California, USA.
Isidro HötzelDepartment of Antibody Engineering, Genentech, Inc., South San Francisco, California, USA.
Kimberly L StarkDepartment of Neuroscience, Genentech, Inc., South San Francisco, California, USA.
Carolina ChouDepartment of Safety Assessment Nonclinical Operations, Genentech, Inc., South San Francisco, California, USA.
Oded ForemanDepartment of Research Pathology, Genentech, Inc., South San Francisco, California, USA.
Amy EastonDepartment of Neuroscience, Genentech, Inc., South San Francisco, California, USA.
Kristin R WildsmithDepartment of Translational Medicine, Genentech, Inc., South San Francisco, California, USA.
Gizette SperindeDepartment of BioAnalytical Sciences, Genentech, Inc., South San Francisco, California, USA.
Christopher M RoseDepartment of Microchemistry, Proteomics, Lipidomics, and Next Generation Sequencing, Genentech, Inc., South San Francisco, California, USA.
Brad A FriedmanDepartment of Bioinformatics, Genentech, Inc., South San Francisco, California, USA.
Reina N FujiDepartment of Safety Assessment Pathology, Genentech, Inc., South San Francisco, California, USA.
Robby M WeimerDepartment of Translational Imaging, Genentech, Inc., South San Francisco, California, USA.
William J MeilandtDepartment of Neuroscience, Genentech, Inc., South San Francisco, California, USA.
Shraddha SadekarDepartment of Preclinical and Translational Pharmacokinetics and Pharmacodynamics, Genentech, Inc., South San Francisco, California, USA.
Alicia A NugentDepartment of Human Pathobiology and OMNI Reverse Translation, Genentech, Inc., South San Francisco, California, USA.
Anne BieverDepartment of Translational Medicine, Genentech, Inc., South San Francisco, California, USA.ORCID 0000-0002-0941-4301

Funding

Genentech, Inc
6 · The paper itself

Abstract

introductionTriggering receptor expressed on myeloid cells 2 (TREM2) agonists are being clinically evaluated as disease-modifying therapeutics for Alzheimer's disease. Clinically translatable pharmacodynamic (PD) biomarkers are needed to confirm drug activity and select the appropriate therapeutic dose in clinical trials.

methodsWe conducted multi-omic analyses on paired non-human primate brain and cerebrospinal fluid (CSF), and stimulation of human induced pluripotent stem cell-derived microglia cultures after TREM2 agonist treatment, followed by validation of candidate fluid PD biomarkers using immunoassays. We immunostained microglia to characterize proliferation and clustering.

resultsWe report CSF soluble TREM2 (sTREM2) and CSF chitinase-3-like protein 1 (CHI3L1/YKL-40) as PD biomarkers for the TREM2 agonist hPara.09. The respective reduction of sTREM2 and elevation of CHI3L1 in brain and CSF after TREM2 agonist treatment correlated with transient microglia proliferation and clustering. DISCUSSION: CSF CHI3L1 and sTREM2 reflect microglial TREM2 agonism and can be used as clinical PD biomarkers to monitor TREM2 activity in the brain. HIGHLIGHTS: CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2) reflects brain target engagement for a novel TREM2 agonist, hPara.09. CSF chitinase-3-like protein 1 reflects microglial TREM2 agonism. Both can be used as clinical fluid biomarkers to monitor TREM2 activity in brain.

Indexed as

BiomarkersBrainChitinase-3-Like Protein 1Membrane GlycoproteinsMicrogliaReceptors, ImmunologicAlzheimer DiseaseAnimalsHumansInduced Pluripotent Stem CellsMaleBiomarkersCHI3L1 protein, humanChitinase-3-Like Protein 1Membrane GlycoproteinsReceptors, ImmunologicTREM2 protein, humanAlzheimer's diseasecerebrospinal fluidchitinase‐3‐like protein 1microgliapharmacodynamic biomarkertriggering receptor expressed on myeloid cells 2

Identifiers

PMID39090679
PMCPMC11497760

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