Evidence for glial-mediated inflammation in aged APPSW transgenic mice

被引：255

作者：

Benzing, WC ^{[1
]}

Wujek, JR

Ward, EK

Shaffer, D

Ashe, KH

Younkin, SG

Brunden, KR

机构：

[1] Gliatech Inc, Cleveland, OH 44122 USA

[2] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA

[3] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA

来源：

NEUROBIOLOGY OF AGING | 1999年 / 20卷 / 06期

关键词：

Alzheimer's disease; animal model; cytokine; glia; IL-1; beta; IL-6; immunocytochemistry; inflammation; mouse; transgenic; TNF;

D O I：

10.1016/S0197-4580(99)00065-2

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Chronic expression of inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6, by glia may underlie the neurodegenerative events that occur within the brains of patients with Alzheimer's disease (AD). The present study determined whether these markers of inflammation could be observed within the brains of Te(HuAPP695.K670N/M67 1L)2576 transgenic mice (Tg2576) that have recently been shown to mimic many features of AD. Interleukin-1 beta- and turner necrosis factor alpha-immunopositive microglia were localized with thioflavine-positive (fibrillar) A beta deposits. Moreover, interleukin-6 immunoreactive astrocytes surrounded fibrillar A beta deposits. These findings provide evidence that Tg2516 mice exhibit features of the inflammatory pathology seen in AD and suggest that these mice are a useful animal model for studying the role inflammation may play in this disease. (C) 2000 Elsevier Science Inc. All rights reserved.

引用

页码：581 / 589

页数：9

共 54 条

[11] MUTATION OF THE BETA-AMYLOID PRECURSOR PROTEIN IN FAMILIAL ALZHEIMERS-DISEASE INCREASES BETA-PROTEIN PRODUCTION [J].

CITRON, M ;

OLTERSDORF, T ;

HAASS, C ;

MCCONLOGUE, L ;

HUNG, AY ;

SEUBERT, P ;

VIGOPELFREY, C ;

LIEBERBURG, I ;

SELKOE, DJ .

NATURE, 1992, 360 (6405) :672-674

[12]

Cole G. M., 1998, Society for Neuroscience Abstracts, V24, P1503

[13]

Combs CK, 1999, J NEUROSCI, V19, P928

[14] Increased amyloid-beta 42(43) in brains of mice expressing mutant presenilin 1 [J].

Duff, K ;

Eckman, C ;

Zehr, C ;

Yu, X ;

Prada, CM ;

Pereztur, J ;

Hutton, M ;

Buee, L ;

Harigaya, Y ;

Yager, D ;

Morgan, D ;

Gordon, MN ;

Holcomb, L ;

Refolo, L ;

Zenk, B ;

Hardy, J ;

Younkin, S .

NATURE, 1996, 383 (6602) :710-713

[15]

ElKhoury J, 1996, NATURE, V382, P716

[16] ELEVATED CIRCULATING TUMOR-NECROSIS-FACTOR LEVELS IN ALZHEIMERS-DISEASE [J].

FILLIT, H ;

DING, W ;

BUEE, L ;

KALMAN, J ;

ALTSTIEL, L ;

LAWLOR, B ;

WOLFKLEIN, G .

NEUROSCIENCE LETTERS, 1991, 129 (02) :318-320

[17]

Frautschy SA, 1998, AM J PATHOL, V152, P307

[18] ALZHEIMER-TYPE NEUROPATHOLOGY IN TRANSGENIC MICE OVEREXPRESSING V717F BETA-AMYLOID PRECURSOR PROTEIN [J].

GAMES, D ;

ADAMS, D ;

ALESSANDRINI, R ;

BARBOUR, R ;

BERTHELETTE, P ;

BLACKWELL, C ;

CARR, T ;

CLEMENS, J ;

DONALDSON, T ;

GILLESPIE, F ;

GUIDO, T ;

HAGOPIAN, S ;

JOHNSONWOOD, K ;

KHAN, K ;

LEE, M ;

LEIBOWITZ, P ;

LIEBERBURG, I ;

LITTLE, S ;

MASLIAH, E ;

MCCONLOGUE, L ;

MONTOYAZAVALA, M ;

MUCKE, L ;

PAGANINI, L ;

PENNIMAN, E ;

POWER, M ;

SCHENK, D ;

SEUBERT, P ;

SNYDER, B ;

SORIANO, F ;

TAN, H ;

VITALE, J ;

WADSWORTH, S ;

WOLOZIN, B ;

ZHAO, J .

NATURE, 1995, 373 (6514) :523-527

[19] Monogenetic determinants of Alzheimer's disease:: APP mutations [J].

Goate, AM .

CELLULAR AND MOLECULAR LIFE SCIENCES, 1998, 54 (09) :897-901

[20]

GRIFFIN WST, 1995, J NEUROPATH EXP NEUR, V54, P276

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