A study published in Nature (DOI: 10.1038/s41593-024-01682-8) reveals that CD8+ T cells contribute to myelin damage in a mouse model of Alzheimer's disease (AD) through the activation of microglia. The research shows that amyloidosis, a hallmark of AD, leads to age-related damage to oligodendrocytes and myelin. Mechanistically, CD8+ T cells promote the accumulation of abnormally interferon-activated microglia, which display myelin-damaging activity. This process is exacerbated by the progressive accumulation of these microglia, leading to increased inflammation and myelin damage. The study also found that CD8+ T cell depletion reduced myelin damage and improved cognitive function in 5xFAD mice, suggesting that targeting immune responses could be a therapeutic strategy for AD. The findings highlight the role of immune cells in driving neurodegenerative diseases with amyloidosis, emphasizing the importance of understanding the interplay between the immune system and myelin pathology in AD. The study used a combination of mouse models, immunohistochemistry, and single-cell RNA sequencing to elucidate the mechanisms underlying the observed effects. The results suggest that targeting inflammation could be a promising approach for delaying the progression of AD.A study published in Nature (DOI: 10.1038/s41593-024-01682-8) reveals that CD8+ T cells contribute to myelin damage in a mouse model of Alzheimer's disease (AD) through the activation of microglia. The research shows that amyloidosis, a hallmark of AD, leads to age-related damage to oligodendrocytes and myelin. Mechanistically, CD8+ T cells promote the accumulation of abnormally interferon-activated microglia, which display myelin-damaging activity. This process is exacerbated by the progressive accumulation of these microglia, leading to increased inflammation and myelin damage. The study also found that CD8+ T cell depletion reduced myelin damage and improved cognitive function in 5xFAD mice, suggesting that targeting immune responses could be a therapeutic strategy for AD. The findings highlight the role of immune cells in driving neurodegenerative diseases with amyloidosis, emphasizing the importance of understanding the interplay between the immune system and myelin pathology in AD. The study used a combination of mouse models, immunohistochemistry, and single-cell RNA sequencing to elucidate the mechanisms underlying the observed effects. The results suggest that targeting inflammation could be a promising approach for delaying the progression of AD.