Shristi Pandey, United States of America
Genentech OMNI BioinformaticsAuthor Of 1 Presentation
DIVERGENT RESPONSES OF MICROGLIA, OLIGODENDROCYTES, ASTROCYTES, AND T CELLS TO TAU, AMYLOID PATHOLOGY, AND TREM2 IN MOUSE MODELS OF ALZHEIMER’S DISEASE
Abstract
Aims
Glial and immune activation in neurodegenerative disease has received increasing attention as an important contributor to disease pathogenesis and progression in Alzheimer’s disease pathology. Here we aim to clarify the individual and collaborative effects of amyloid and tau pathology on responses of glial and immune cells in the brain.
Methods
We study cellular level changes of hippocampal cells by untargeted single cell RNA-seq using different AD mouse models that capture tau pathology, amyloid pathology, or combined pathology. We also examine how these disease-associated glial changes are affected by TREM2. We utilize in situ hybridization to corroborate major findings from single cell RNA-seq and to examine spatial distribution of gene expression changes in different cells.
Results
We observe distinct responses of microglia, astrocytes, oligodendrocytes and T cells to tau, Aβ or combined pathology. Interestingly, the disease-associated oligodendrocyte and astrocyte changes we observe show little dependence on TREM2 while the majority of microglial responses are dampened in Trem2 knockout mice.
Conclusions
Our study highlights distinct transcriptional states of microglia, oligodendrocytes, astrocytes, and T cells in the degenerating brain and how they are influenced by amyloidosis and a key Alzheimer’s Disease risk gene, Trem2. Our study may help identify diagnostic biomarkers and therapeutic targets related to disease progression.