Neuroinflammation-induced acceleration of amyloid deposition in the APPV717F transgenic mouse.
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 APPV717F+/+ 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 Abeta deposits revealed a marked acceleration of amyloid deposition in LPS-treated APPV717F+/+-apoE+/+ mice compared to nontreated or vehicle-treated APPV717F+/+-apoE+/+ mice (P = 0.005). By contrast, no amyloid deposits were detected by thioflavine-S staining in LPS or vehicle-treated apoE-deficient APPV717F TG mice. Our data suggest that neuroinflammation can accelerate amyloid deposition in the APPV717F+/+ mouse model of AD and that this process requires the expression of apoE.
Qiao
X
X
Department of Cellular Biology & Anatomy, Louisiana State University Medical Center, Shreveport, LA 71130, USA.
Cummins
D J
DJ
Paul
S M
SM
D000682:Amyloid / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D052160:Benzothiazoles; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism*; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D013844:Thiazoles
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013844:Thiazoles; C009462:thioflavin T