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Neuroinflammation‐induced acceleration of amyloid deposition in the APP V717F transgenic mouse
Author(s) -
Qiao Xiaoxi,
Cummins David J.,
Paul Steven M.
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01666.x
Subject(s) - neuroinflammation , genetically modified mouse , amyloid precursor protein , apolipoprotein e , immunostaining , amyloid (mycology) , lipopolysaccharide , astrocytosis , transgene , microglia , chemistry , biology , alzheimer's disease , endocrinology , pathology , immunology , medicine , inflammation , immunohistochemistry , biochemistry , disease , gene
It has been postulated that neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease (AD). To directly test whether an inflammatory stimulus can accelerate amyloid deposition in vivo , we chronically administered the bacterial endotoxin, lipopolysaccharide (LPS), intracerebroventricularly (i.c.v.) to 2‐month‐old APP V717F+/+ transgenic (TG) mice, which overexpress a mutant human amyloid precursor protein (APP 717V‐F) with or without apolipoprotein E (apoE) for 2 weeks. Two weeks following central LPS administration a striking global reactive astrocytosis with increased GFAP immunoreactivity was found throughout the brains of all LPS‐treated wild‐type and transgenic mice including the contralateral brain hemisphere. Localized microglial activation was also evident from lectin immunostaining adjacent to the cannula track of LPS‐treated mice. Quantification of thioflavine‐S‐positive Aβ deposits revealed a marked acceleration of amyloid deposition in LPS‐treated APP V717F+/+ –apoE +/+ mice compared to nontreated or vehicle‐treated APP V717F+/+ –apoE +/+ mice ( P = 0.005). By contrast, no amyloid deposits were detected by thioflavine‐S staining in LPS or vehicle‐treated apoE‐deficient APP V717F TG mice. Our data suggest that neuroinflammation can accelerate amyloid deposition in the APP V717F+/+ mouse model of AD and that this process requires the expression of apoE.