Shinkei Kenkyu no Shinpo Volume 49, Issue 3 (June 2005)
Japanese

Alzheimer's disease and microglia Haruhiko Akiyama 1 1Department of Psychogeriatrics, Tokyo Institute of Psychiatry Keyword: アミロイドβ蛋白質除去 , 神経炎症 , 神経毒性 pp.347-356
Published Date 2005/6/10
DOI https://doi.org/10.11477/mf.1431100052
  • Abstract
  • Look Inside

Lesions of Alzheimer disease(AD) are associated with low-grade but sustained inflammatory responses. Activated microglia play a major role for the neuroinflammation in AD. Upon activation, microglia are known to secrete a wide variety of molecules involved in inflammation, many of which are potentially neurotoxic. Activated microglia could be targets of anti-inflammatory therapy of AD. However, evidence also indicates that microglia eliminate Aβ from the brain. Aβ is produced continuously in both the normal and the AD brain. Under normal conditions, Aβ is removed successfully before it accumulates as extracellular amyloid fibrils. Even in AD, a large portion of Aβ may be cleared from the brain with a small portion being left and deposited as neurotoxic senile plaques. Both in vivo and in vitro studies have shown the effective uptake of soluble Aβ by microglia. Microglia seem to be involved, without significant activation, in the removal of Aβ before it is deposited extracellularly. Aβ, once deposited as insoluble fibrils, is also removed by microglia. In the AD cerebral cortex complicated with recent infarction, activated microglia and monocyte-derived macrophages remove the necrotic tissue debris. Phogocytic removal of Aβ by microglia is also upregulated in areas with incomplete ischemia where neuropil is preserved and neurons survive. In some cases, such upregulation of microglial activity appears to result in the complete clearance of Aβ from the neuropil. Activated microglia agglomerated in senile plaques phagocytose the Aβ deposits. In AD without complication, however, the elimination is at best partial. Further activation of microglia may be beneficial to Aβ removal but can also be hazardous to neurons. Appropriate regulation of microglial activity could be a promising strategy to develop effective therapy of AD.


Copyright © 2005, Igaku-Shoin Ltd. All rights reserved.

基本情報

00018724.49.3.jpg
神経研究の進歩
49巻3号 (2005年6月)
電子版ISSN 1882-1243 印刷版ISSN 0001-8724 医学書院

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