Work

Xenografted human microglia display diverse transcriptomic states in response to Alzheimer’s disease‐related Aβ pathology

Year: 2024

Type: article

Abstract: Background Microglia are central players in Alzheimer’s Disease (AD) pathology, but analyzing microglia states in human brain samples is challenging due to genetic diversity, postmortem delay and admixture of pathologies. Method To circumvent these issues, here we collected 138,577 single cell expression profiles of human stem cell derived‐microglia from a xenotransplantation model of AD. Result Xenografted human microglia adopt a disease‐associated (DAM) profile similar to that seen in mouse microglia, but display a more pronounced HLA state, likely related to antigen presentation in response to amyloid plaques. The human microglial response also involves a pro‐inflammatory cytokine/chemokine CRM response to oligomeric Aβo. Expression of AD risk genes is distributed over this multi‐pronged response to amyloid pathology. Genetic deletion of TREM2 or APOE, as well as APOE polymorphisms and TREM2R47H expression in the transplanted microglia modulate these responses differentially. Conclusion We have identified multiple transcriptomic cell states adopted by microglia in response to AD‐related pathology, which should be taken into account in translational studies.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.090394

Author: Renzo Mancuso

Institution: Vlaams Instituut voor Biotechnologie

Language: English

Topic: Neuroinflammation and Neurodegeneration Mechanisms

Subfield: Neurology

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,000