Risk of Alzheimer's disease and duration of NSAID use

Stewart, WF; Kawas, Claudia H.; Corrada, María M.; Ej, Metter

doi:10.1212/wnl.48.3.626

Cited by 1,040 publications

(616 citation statements)

References 10 publications

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“…Therefore, COX inhibitors may be useful drugs to treat or retard the progression of Alzheimer's disease. Numerous clinical trials have examined the therapeutic benefit of COX inhibitors in Alzheimer's patients with the best success in patients treated early during disease progression and when used for more than 24 months (Stewart et al, 1997;in't Veld et al, 2001). Similarly, animal studies with aged rats demonstrate that PGs can be elevated with normal aging and COX inhibitors can reverse age-related memory impairments (Casolini et al, 2002;Mesches et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Prostaglandins are necessary and sufficient to induce contextual fear learning impairments after interleukin-1 beta injections into the dorsal hippocampus

et al. 2007

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The intra-hippocampal administration of interleukin-1β (IL-1β) as well as the induction of elevated but physiological levels of IL-1β within the hippocampus interferes with the formation of long-term memory. There is evidence suggesting that the induction of prostaglandin (PG) formation by IL-1β is involved in impairments in working and spatial memory following IL-1β. The present experiments extend these findings by showing that PGs are responsible for memory deficits in contextual fear conditioning that occur following IL-1β injection into the dorsal hippocampus. Cyclooxygenase (COX) inhibition blocked the disruption in contextual fear conditioning produced by IL-1β and COX inhibition alone also disrupted contextual memory, suggesting an inverted Ushaped relationship between PG levels and memory. In addition to demonstrating the necessity of PGs in IL-1β mediated memory deficits, we also show that PGs injected directly into the dorsal hippocampus are sufficient to impair context memory and significantly reduce post-conditioning levels of BDNF within the hippocampus, suggesting a possible mechanism for the memory-impairing effects of PGs. Keywords memory; brain derived neurotrophic factor; cyclooxygenase; EP receptorThe pro-inflammatory cytokine interleukin-1β (IL-1β) exerts powerful central and peripheral actions. Recently, there has been considerable interest in its influence within the brain on learning and memory. This interest initially derived in part from findings that Alzheimer's disease and AIDS-related dementia are associated with elevated brain levels of IL-1β (Griffen et al., 1989;Lombardi et al., 1999). More direct evidence implicating IL-1β in learning and memory has come from animal studies. Manipulations that increase levels of IL-1β within the hippocampus have been shown to impair memory formation. These manipulations include the injection of the gram-negative bacterial component lipopolysaccharide (LPS;Pugh et al. 1998), social isolation stress (Pugh et al., 1999), and aging (Gemma et al., 2005). The blockade of IL-1 receptors and/or the inhibition of IL-1 synthesis prevents these memory impairments, supporting the conclusion that they are mediated by IL-1β (Pugh et al. 1998;Pugh et al., 1999;Gemma et al., 2005). Moreover, direct injection of IL-1β into the dorsal hippocampus Tel.: +1 303 492 9616; fax: +1 303 492 2967., E-mail address: amy.hein@colorado.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Barrientos et al., 2002). Consistent with these data, IL-1β potently inhibits long-term potentiation (LTP), a form of synaptic strengthenin...

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Section: Discussionmentioning

confidence: 99%

Prostaglandins are necessary and sufficient to induce contextual fear learning impairments after interleukin-1 beta injections into the dorsal hippocampus

et al. 2007

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“…Recent evidence suggests that inflammatory processes play an active role in AD; epidemiological studies reported that the use of nonsteroidal anti-inflammatory drugs is associated with marked reduction in the risk of AD ( [106,154,156,219,225]). Following this initial observation, additional reports were published that witnessed the involvement of neuroinflammation in AD pathogenesis and progression.…”

Section: Alzheimer's Disease and Neuroinflammationmentioning

confidence: 99%

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Vegeto

Benedusi

Maggi

2008

Frontiers in Neuroendocrinology

271

206

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a b s t r a c tRecent studies highlight the prominent role played by estrogens in protecting the central nervous system (CNS) against the noxious consequences of a chronic inflammatory reaction. The neurodegenerative process of several CNS diseases, including Multiple Sclerosis, Alzheimer's and Parkinson's Diseases, is associated with the activation of microglia cells, which drive the resident inflammatory response. Chronically stimulated during neurodegeneration, microglia cells are thought to provide detrimental effects on surrounding neurons. The inhibitory activity of estrogens on neuroinflammation and specifically on microglia might thus be considered as a beneficial therapeutic opportunity for delaying the onset or progression of neurodegenerative diseases; in addition, understanding the peculiar activity of this female hormone on inflammatory signalling pathways will possibly lead to the development of selected anti-inflammatory molecules. This review summarises the evidence for the involvement of microglia in neuroinflammation and the anti-inflammatory activity played by estrogens specifically in microglia.

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“…[85][86][87][88] Some also argue that NSAIDs have no effect in patients already suspected to have developed AD 89 and that treatment with a COX-2 inhibitor increases the amount of b-amyloid found in the brain. 90 One must note that inhibition of COX-2 in the CNS has proinflammatory properties.…”

Section: Innate Immunity and Alzheimer's Diseasementioning

confidence: 99%

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

2006

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The role of innate immunity and microglia in the brain is currently a matter of great debate and controversy. While several studies have provided evidence that they contribute to neurodegeneration in various animal models of brain diseases and traumas, others have shown that their inhibition may in contrast be associated with more damages or less repair. We have recently reported the existence of two different types of microglia, the resident and the newly differentiated microglia that derive from the bone marrow stem cells. Of great interest is the fact that blood-derived microglial cells are associated with amyloid plaques and these cells are able to prevent the formation or eliminate the presence of amyloid deposits in mice that develop the major hallmark of Alzheimer's disease (AD). These newly recruited cells are specifically attracted to the b-amyloid 40/42 isoforms in vivo and they participate in the elimination of these proteins by phagocytosis. This review presents the mechanisms involved in the control of the innate immune response by microglia and the beneficial properties of such a response in brain diseases, such as AD.

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Risk of Alzheimer's disease and duration of NSAID use

Cited by 1,040 publications

References 10 publications

Prostaglandins are necessary and sufficient to induce contextual fear learning impairments after interleukin-1 beta injections into the dorsal hippocampus

Prostaglandins are necessary and sufficient to induce contextual fear learning impairments after interleukin-1 beta injections into the dorsal hippocampus

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

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