The importance of the complement system in Alzheimer's disease (AD) pathogenesis has been emphasized through recent genome wide association studies. However, the cellular and molecular role of these complement proteins is not fully understood. Microglia express complement receptors and the activation of specific receptors may increase Aβ clearance and reduce neurodegeneration. Here, we investigated the contribution of complement receptor 1 (CR1), the second most significant hit in GWAS studies, on microglia to neuronal damage. We show that microglia displaying an activated phenotype demonstrate an increase in CR1 expression. We also provide evidence that activation of microglial CR1 was detrimental to neurons and this correlated with an increase in microglial intracellular superoxide generation, and tumour necrosis factor-α (TNFα) and interleukin-1 β (IL-1β) secretion. Amyloid-β 42 (Aβ1-42)-treated microglia displayed an increased ability to phagocytose dextran beads following antibody blockage of CR1 but a decreased capacity to phagocytose fluorescent-tagged Aβ1-42. Together, these results indicate that microglial CR1 plays a role in the neuronal death observed in AD and investigating this further may provide a possible strategy to control neurotoxicity in the AD brain.
Alzheimer disease (AD) is the most common form of neurodegenerative disease, estimated to contribute 60-70% of all cases of dementia worldwide. According to the prevailing amylo...
Abstract There is now abundant evidence that brain microglia, when activated, have the lineage, receptors, and synthetic capacity to participate in both potentially neurotoxic i...
The contribution of inflammation to the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, and prion diseases is poorly understood. Brain inflammation i...
Currently, 47 million people live with dementia globally, and it is estimated to increase more than threefold (~131 million) by 2050. Alzheimer's disease (AD) is one of the majo...
Neuroinflammation mediated by microglial activation appears to play an essential role in the pathogenesis of Parkinson disease; however, the mechanisms by which microglia are ac...
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