Cell mediators of inflammation in the Alzheimer disease brain.
Lesions of Alzheimer disease are associated with low-grade but sustained inflammatory responses. Activated microglia agglomerate in the center of senile plaques. Reactive astrocytes marginate the amyloid beta-protein (A beta) deposits and extend their processes toward the center of plaques. Both microglia and astrocytes are known to secrete a wide variety of molecules involved in inflammation and are potential sources of proinflammatory elements in the brain. Dystrophic neurites occur in senile plaques with such glial reactions, suggesting the relevance of inflammatory responses to the neuronal degeneration in Alzheimer disease. Activated glial cells are, therefore, targets of anti-inflammatory therapy of Alzheimer disease. However, evidence also indicates that these cells eliminate A beta from the brain. A beta is produced continuously in both the normal and the AD brain. Under normal conditions, A beta is removed successfully before it accumulates as extracellular amyloid fibrils. Even in Alzheimer disease, a large portion of A beta 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 showed the effective uptake of A beta by microglia. Before clinical application, it must be determined whether the treatment that suppresses glial activation and inflammatory responses inhibits A beta removal by glial cells.
Akiyama
H
H
Tokyo Institute of Psychiatry, Japan.
Arai
T
T
Kondo
H
H
Tanno
E
E
Haga
C
C
Ikeda
K
K
D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001253:Astrocytes / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D017628:Microglia / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology*
D016229:Amyloid beta-Peptides; D018799:Intercellular Adhesion Molecule-1