Clinical aspects of inflammation in Alzheimer's disease.
In Alzheimer's disease (AD) there is increasing evidence that neurotoxicity is mediated by CNS inflammatory processes. These processes involve activation of microglia by amyloid-beta leading to release of pro-inflammatory cytokines including IL-1beta, IL-6, and TNF-alpha among others. Neurotoxic processes mediated by these cytokines may include direct neuronal death by enhancement of apoptosis, decreased synaptic function as evidence by inhibition of long-term potentiation, and inhibition of hippocampal neurogenesis. Central nervous system (CNS) inflammation may predate the development of senile plaques and neurofibrillary tangles in AD and may prove to be a more sensitive marker of prodromal AD. New developments in measuring CNS inflammation include measuring cytokine release by peripheral blood mononuclear cells and the development of PET markers of microglial activation. There is epidemiological evidence that circulating serum IL-6 is associated with poorer cognition. While epidemiological studies suggest a protective effect of NSAIDs against development of AD, controlled trials of NSAIDs to date have not shown any protective effect of drug. New anti-inflammatory agents for treating or preventing AD may include novel NSAIDs and opioid antagonists. These developments provide an alternative or potential adjunct to anti-amyloid therapies for AD.
Rosenberg
Paul B
PB
Division of Geriatric Psychiatry and Neuropsychiatry, John Hopkins University School of Medicine, Baltimore, MD 21205, USA. prosenb9@jhmi.edu
D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000276:immunology; D006624:Hippocampus / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D017628:Microglia / Q000276:immunology; D016874:Neurofibrillary Tangles / Q000276:immunology; D009474:Neurons / Q000276:immunology; D058225:Plaque, Amyloid / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators