A microglial activity state biomarker panel differentiates FTD-granulin and Alzheimer's disease patients from controls.

ABSTRACT:

Background

With the emergence of microglia-modulating therapies there is an urgent need for reliable biomarkers to evaluate microglial activation states.

Methods

Using mouse models and human induced pluripotent stem cell-derived microglia (hiMGL), genetically modified to yield the most opposite homeostatic (TREM2-knockout) and disease-associated (GRN-knockout) states, we identified microglia activity-dependent markers. Non-targeted mass spectrometry was used to identify proteomic changes in microglia and cerebrospinal fluid (CSF) of Grn- and Trem2-knockout mice. Additionally, we analyzed the proteome of GRN- and TREM2-knockout hiMGL and their conditioned media. Candidate marker proteins were tested in two independent patient cohorts, the ALLFTD cohort (GRN mutation carriers

SUBMITTER: Pesamaa I 

PROVIDER: S-EPMC10543321 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature