Microglia actions in Alzheimer’s disease.
The identification of microglia-associated, neurological disease-causing mutations in patients, combined with studies in mouse models has highlighted microglia, the brain’s intrinsic myeloid cells, as key modulators of pathogenesis and disease progression in neurodegenerative diseases. In Alzheimer’s disease (AD) in particular, the activation and accumulation of microglial cells around b-Amyloid (Ab) plaques has long been described and is believed to result in chronic neuroinflammation—a term that, despite being commonly used, lacks a precise definition. This seemingly directed response of microglia to amyloid deposits conflicts with the fact that the increasing buildup of Ab plaques is not inhibited by these cells during disease progression. While recent evidence suggests that microglia lose their intrinsic beneficial function during the course of AD and may even acquire a ‘‘toxic’’ phenotype over time, Ab may also simply not be an appropriate trigger to induce phagocytosis and degradation by microglia in vivo. As recent experimental evidence has indicated the importance of the microglia in AD pathogenesis, future efforts aimed at tackling this disease via utilization or modulation of microglia or factors therefrom appear to be an exciting and challenging research front.
Stefan
S
Prokop
Kelly R
KR
Miller
Frank L
FL
Heppner
D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D023582:Alzheimer Vaccines / Q000627:therapeutic use; D016229:Amyloid beta-Peptides / Q000276:immunology; D000818:Animals; D016922:Cellular Senescence / Q000502:physiology; D006801:Humans; D008262:Macrophage Activation / Q000502:physiology; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D022423:Myeloid Cells / Q000502:physiology; D010641:Phenotype
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides