Lipopolysaccharide-induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid β peptide in APPswe transgenic mice

Jin G Sheng; Susan H Bora; G Xu; David R Borchelt; Donald L Price; Vassilis E Koliatsos

Neurobiology of Disease (Oct 2003)

Lipopolysaccharide-induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid β peptide in APPswe transgenic mice

Jin G Sheng,
Susan H Bora,
G Xu,
David R Borchelt,
Donald L Price,
Vassilis E Koliatsos

Affiliations

Jin G Sheng: Department of Pathology (Division of Neuropathology), The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology and Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Susan H Bora: Department of Pathology (Division of Neuropathology), The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology and Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
G Xu: Department of Pathology (Division of Neuropathology), The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology and Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
David R Borchelt: Department of Pathology (Division of Neuropathology), The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology and Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Donald L Price: Department of Pathology (Division of Neuropathology), The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology and Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Vassilis E Koliatsos: Department of Pathology (Division of Neuropathology), The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology and Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

Journal volume & issue: Vol. 14, no. 1
pp. 133 – 145

Abstract

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The present study was designed to examine whether brain inflammation caused by systemic administration of lipopolysaccharides (LPS) alters the expression/processing of amyloid precursor protein (APP) and increases the generation of amyloid β peptide (Aβ). APPswe transgenic (Tg) mice were treated with either LPS or phosphate-buffered saline (PBS). In LPS-treated APPswe mice, Aβ1–40/42 was 3-fold and APP was 1.8-fold higher than those in PBS-treated mice (P < 0.05) by ELISA, Western blots and immunoprecipitation–mass spectrometry (IP–MS) ProteinChip analysis. Numbers of Aβ- and APP-immunoreactive neurons (Aβ(+) and APP(+) neurons) increased significantly in LPS-treated APPswe mice; APP(+) and Aβ(+) neurons in neocortex were associated with an increased number of F4/80-immunoreactive microglia (F4/80(+) microglia) in their anatomical environment. Our findings demonstrate that experimental neuroinflammation increases APP expression/processing and causes intracellular accumulation of Aβ. It remains to be seen whether such events can cause neuronal dysfunction/degeneration and, with time, lead to extracellular Aβ deposits, as they occur in Alzheimer’s disease.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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