title: Microglia as a potential bridge between the amyloid beta-peptide and tau.
abstract: Inflammation is a critical component of the pathogenesis of Alzheimer's disease (AD), consisting of the activation of both microglia and astrocytes. Activated microglia and reactive astrocytes are found in and around extraneuronal amyloid-beta plaques and are thought to facilitate the clearance of these deposits from the brain parenchyma. However, mounting evidence indicates that chronic activation of microglia, presumably via the secretion of cytokines and reactive molecules, may exacerbate plaque pathology as well as enhance the hyperphosphorylation of tau and the subsequent development of neurofibrillary tangles. Thus, suppression of microglial activity in AD brain has been considered as a potential treatment of AD and may slow the disease progression. Along these lines, anti-inflammatory drugs, particularly nonsteroidal anti-inflammatory drugs (NSAIDs), lessen the effects of AD pathology. In this review, we discuss the molecular mechanism of inflammatory responses in AD brain as well as animal models, and current therapies using NSAIDs, antioxidants, and immunotherapy as neuroprotective strategies for AD.
authors.affiliation: Laboratory of Molecular Neuropathogenesis, Department of Neurobiology and Behavior, University of California, Irvine, 92697-4545, USA.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kitazawa
authors.forename: Tritia R
authors.initials: TR
authors.lastname: Yamasaki
authors.forename: Frank M
authors.initials: FM
authors.lastname: LaFerla
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D017628:Microglia / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010455:Peptides; D016875:tau Proteins