Microglia and Beyond

Download or read book Microglia and Beyond written by and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Summary This thesis describes multiple central and peripheral immune cell changes during aging, in Alzheimer’s disease (AD), and multiple sclerosis (MS). In the first chapters of this thesis, we investigated the effect of aging on the immune system and searched for the aging factors involved. In the later chapters, we investigated the immune response to AD and MS pathology. Aging During aging, a general decline in immune function occurs, ultimately contributing to increased susceptibility to infections in the elderly. We found that microglial morphological complexity declines during aging and can be modulated by peripheral levels of glucocorticoids. We further discovered that peripheral factors can induce age-associated changes in the brain, and thus potentially counteract them. Consequently, we hypothesize that modulating peripheral immunity via plasma factors, such as hormones and cytokines, could combat brain aging and associated pathology. Alzheimer’s disease AD is a neurodegenerative disease that ultimately causes dementia. One of the pathological hallmarks is the deposition of abnormal tau protein in the brain. We found that this deposition induced reactive and dystrophic microglia with increased lysosomal volumes containing abnormal tau and postsynaptic structures. Together, this shows that tauopathy induces a loss of homeostatic microglia that is potentially linked to a loss of synapses. Peripheral immune cells are associated with neurodegenerative diseases as well, although fewer research attempts have investigated these cells in the context of AD. We analyzed the peripheral immune landscape of AD patients at the early and late stages of the disease and found that levels of circulating CD8+ T cells with an effector memory phenotype increased before the onset of dementia. These CD8+ T cells expressed markers associated with T cell senescence and terminal differentiation.