TY - JOUR
T1 - Clinical aspects of inflammation in Alzheimer's disease
AU - Rosenberg, Paul B.
PY - 2005/12
Y1 - 2005/12
N2 - 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-β leading to release of pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α 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.
AB - 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-β leading to release of pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α 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.
UR - http://www.scopus.com/inward/record.url?scp=30644479192&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=30644479192&partnerID=8YFLogxK
U2 - 10.1080/02646830500382037
DO - 10.1080/02646830500382037
M3 - Review article
C2 - 16401549
AN - SCOPUS:30644479192
SN - 0954-0261
VL - 17
SP - 503
EP - 514
JO - International Review of Psychiatry
JF - International Review of Psychiatry
IS - 6
ER -