T cell mediated microglia activation triggers myelin pathology in a model of amyloidosis
Age-related myelin damage induces inflammatory responses, yet its involvement in Alzheimer's disease (AD) remains uncertain, despite age being a major risk factor. Using a mouse model of AD, we found that amyloidosis itself triggers age-related oligodendrocyte and myelin damage. Mechanistically, CD8+ T cells promote the progressive accumulation of abnormally interferon-activated microglia that display myelin-damaging activity. Thus, immune responses against myelinating oligodendrocytes may contribute to neurodegenerative diseases with amyloidosis. Overall design: To determine whether CD8+ T cells contribute to oligodendrocyte and myelin pathology in 5xFAD mice, we treated 6-months old 5xFAD mice with antibodies against CD8. For the depletion of CD8+ T cells mice, 5xFAD mice aged 6 months were intraperitoneally injected with anti-CD8 antibody (BioXCell, BP0061) and their respective isotype controls (BioXCell, BE0119) twice a week for a total of 6 weeks.For 10X genomic experiments, mice were deeply anesthetized and perfused with cold PBS. Each brain was removed and individually microdissected under a dissection microscope, wherein the cortex and hippocampus were isolated from the brain and the attached choroid plexus was removed.