Inflammation and cerebral amyloidosis are disconnected in an animal model of Alzheimer's disease

Joseph Quinn; Thomas Montine; Jason Morrow; William R. Woodward; Doris Kulhanek; Felix Eckenstein

doi:10.1016/S0165-5728(03)00037-7

Inflammation and cerebral amyloidosis are disconnected in an animal model of Alzheimer's disease

Joseph Quinn, Thomas Montine, Jason Morrow, William R. Woodward, Doris Kulhanek, Felix Eckenstein

Research output: Contribution to journal › Article › peer-review

98 Scopus citations

Abstract

The hypothesis that inflammation and beta amyloid deposition are causally linked in Alzheimer's disease (AD) was tested in a transgenic mouse model. Untreated beta amyloid plaque-bearing Tg2576 mice did not differ from wild type animals in brain levels of most inflammatory mediators. Indomethacin treatment suppressed brain levels of prostaglandins by 90%, but reduced hippocampal beta amyloid by only 20%, with no effect on cortical beta amyloid. The discordant effects on beta amyloid and cyclooxygenase (COX) suggest that these effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are not causally linked. Further evidence against a causal relationship is seen in an unexpected trend to lower levels of beta amyloid after an inflammatory stimulus [lipopolysaccharide (LPS)].

Original language	English (US)
Pages (from-to)	32-41
Number of pages	10
Journal	Journal of Neuroimmunology
Volume	137
Issue number	1-2
DOIs	https://doi.org/10.1016/S0165-5728(03)00037-7
State	Published - Apr 2003

Keywords

Alzheimer
Animal model
Cyclooxygenase
F2-isoprostanes
Indomethacin
Nonsteroidal anti-inflammatory drug
Oxidative stress

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Neurology
Clinical Neurology

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10.1016/S0165-5728(03)00037-7

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title = "Inflammation and cerebral amyloidosis are disconnected in an animal model of Alzheimer's disease",

abstract = "The hypothesis that inflammation and beta amyloid deposition are causally linked in Alzheimer's disease (AD) was tested in a transgenic mouse model. Untreated beta amyloid plaque-bearing Tg2576 mice did not differ from wild type animals in brain levels of most inflammatory mediators. Indomethacin treatment suppressed brain levels of prostaglandins by 90%, but reduced hippocampal beta amyloid by only 20%, with no effect on cortical beta amyloid. The discordant effects on beta amyloid and cyclooxygenase (COX) suggest that these effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are not causally linked. Further evidence against a causal relationship is seen in an unexpected trend to lower levels of beta amyloid after an inflammatory stimulus [lipopolysaccharide (LPS)].",

keywords = "Alzheimer, Animal model, Cyclooxygenase, F2-isoprostanes, Indomethacin, Nonsteroidal anti-inflammatory drug, Oxidative stress",

author = "Joseph Quinn and Thomas Montine and Jason Morrow and Woodward, {William R.} and Doris Kulhanek and Felix Eckenstein",

note = "Funding Information: The authors wish to thank Dr. Karen Hsiao-Aske for the gift of Tg2576 mice, Byron Care for his assistance with preparation of figures and Richard Jones PhD, for his valuable discussions. This work was supported by the Department of Veteran's Affairs, NIA-AG07424, NIH-AG08017, NIH-AT00066-01, NIH-AG00774, NIHAG16835.",

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doi = "10.1016/S0165-5728(03)00037-7",

language = "English (US)",

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AU - Quinn, Joseph

AU - Montine, Thomas

AU - Morrow, Jason

AU - Woodward, William R.

AU - Kulhanek, Doris

AU - Eckenstein, Felix

N1 - Funding Information: The authors wish to thank Dr. Karen Hsiao-Aske for the gift of Tg2576 mice, Byron Care for his assistance with preparation of figures and Richard Jones PhD, for his valuable discussions. This work was supported by the Department of Veteran's Affairs, NIA-AG07424, NIH-AG08017, NIH-AT00066-01, NIH-AG00774, NIHAG16835.

PY - 2003/4

Y1 - 2003/4

N2 - The hypothesis that inflammation and beta amyloid deposition are causally linked in Alzheimer's disease (AD) was tested in a transgenic mouse model. Untreated beta amyloid plaque-bearing Tg2576 mice did not differ from wild type animals in brain levels of most inflammatory mediators. Indomethacin treatment suppressed brain levels of prostaglandins by 90%, but reduced hippocampal beta amyloid by only 20%, with no effect on cortical beta amyloid. The discordant effects on beta amyloid and cyclooxygenase (COX) suggest that these effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are not causally linked. Further evidence against a causal relationship is seen in an unexpected trend to lower levels of beta amyloid after an inflammatory stimulus [lipopolysaccharide (LPS)].

AB - The hypothesis that inflammation and beta amyloid deposition are causally linked in Alzheimer's disease (AD) was tested in a transgenic mouse model. Untreated beta amyloid plaque-bearing Tg2576 mice did not differ from wild type animals in brain levels of most inflammatory mediators. Indomethacin treatment suppressed brain levels of prostaglandins by 90%, but reduced hippocampal beta amyloid by only 20%, with no effect on cortical beta amyloid. The discordant effects on beta amyloid and cyclooxygenase (COX) suggest that these effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are not causally linked. Further evidence against a causal relationship is seen in an unexpected trend to lower levels of beta amyloid after an inflammatory stimulus [lipopolysaccharide (LPS)].

KW - Alzheimer

KW - Animal model

KW - Cyclooxygenase

KW - F2-isoprostanes

KW - Indomethacin

KW - Nonsteroidal anti-inflammatory drug

KW - Oxidative stress

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Inflammation and cerebral amyloidosis are disconnected in an animal model of Alzheimer's disease

Abstract

Keywords

ASJC Scopus subject areas

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