Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 33, Issue -, Pages 24-28Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2013.05.002
Keywords
Lipopolysaccharide; Cytokines; Amyloid-beta; Alzheimer's disease; Memory
Categories
Funding
- Texas Higher Education Coordinating Board [NHARP9424]
- Texas Christian University [RCAF60675]
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Alzheimer's disease (AD) is characterized, in part, by atrophy of the adult brain and increased presence of extracellular amyloid-beta (A beta) plaques. Previous studies in our lab have shown that peripheral inflammation can lead to increased central A beta and deficits in learning and memory. In order to determine whether A beta accumulation in the brain is responsible for the learning deficits, we attempted to decrease peripheral production of A beta in order to reduce central A beta accumulation. It has previously been shown that A beta is produced in large quantities in the liver, and is transferred across the blood-brain barrier (BBB). Recent research has shown that peripheral treatment with imatinib methanesulfonate salt (IM), known to interfere with the interaction between gamma (gamma)-secretase and the gamma-secretase activating protein (GSAP), decreases the cleavage of peripheral amyloid precursor protein into A beta. Because IM poorly penetrates the BBB, we hypothesized that co-administration of IM with LPS would decrease peripheral production of A beta in the presence of LPS-induced inflammation, leading to a decrease in A beta accumulation in the hippocampus. We show that peripheral IM treatment eliminates hippocampal A beta elevation that follows LPS-induced peripheral inflammation. Importantly, IM also eliminates the cognitive impairment seen following seven consecutive days of LPS administration, implicating A beta peptides as a likely cause of these cognitive deficits. (c) 2013 Elsevier Inc. All rights reserved.
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