The role of inflammation in Alzheimer's disease.
Considerable evidence gained over the past decade has supported the conclusion that neuroinflammation is associated with Alzheimer's disease (AD) pathology. Inflammatory components related to AD neuroinflammation include brain cells such as microglia and astrocytes, the classic and alternate pathways of the complement system, the pentraxin acute-phase proteins, neuronal-type nicotinic acetylcholine receptors (AChRs), peroxisomal proliferators-activated receptors (PPARs), as well as cytokines and chemokines. Both the microglia and astrocytes have been shown to generate beta-amyloid protein (Abeta), one of the main pathologic features of AD. Abeta itself has been shown to act as a pro-inflammatory agent causing the activation of many of the inflammatory components. Further substantiation for the role of neuroinflammation in AD has come from studies that demonstrate patients who took non-steroidal anti-inflammatory drugs had a lower risk of AD than those who did not. These same results have led to increased interest in pursuing anti-inflammatory therapy for AD but with poor results. On the other hand, increasing amount of data suggest that AChRs and PPARs are involved in AD-induced neuroinflammation and in this regard, future therapy may focus on their specific targeting in the AD brain.
Center for Aging, University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine, Stratford, NJ 08084, USA. tuppoee@umdnj.edu
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D000209:Acute-Phase Proteins / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016503:Drug Delivery Systems; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism
D000209:Acute-Phase Proteins; D016564:Amyloid beta-Protein Precursor; D000894:Anti-Inflammatory Agents, Non-Steroidal; D047492:Peroxisome Proliferator-Activated Receptors; D011978:Receptors, Nicotinic