Primate cerebrospinal fluid CHI3L1 reflects brain TREM2 agonism.

ABSTRACT:

Introduction

Triggering 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.

Methods

We 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.

Results

We report CSF soluble TREM2 (sTREM2) and CSF chitinase-3-like protein 1 (CHI3

SUBMITTER: Schauer SP 

PROVIDER: S-EPMC11497760 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature