%0 Journal Article
%T Lipopolysaccharide endotoxemia induces amyloid-¦Â and p-tau formation in the rat brain
%A Ahmed H Ebada Salem
%A Fernando A Bozza
%A Jeffrey T Yap
%A John M Hoffman
%A Joshua A Sonnen
%A Kathryn A Morton
%A Kevin P Horn
%A Li-Ming Wang
%A Qi Wu
%A Rheal A Towner
%A Rosana S Rodrigues
%A Ryan A Kirk
%J Archive of "American Journal of Nuclear Medicine and Molecular Imaging".
%D 2018
%X Amyloid beta (A¦Â) plaques are not specific to Alzheimer¡¯s disease and occur with aging and neurodegenerative disorders. Soluble brain A¦Â may be neuroprotective and increases in response to neuroinflammation. Sepsis is associated with neurocognitive compromise. The objective was to determine, in a rat endotoxemia model of sepsis, whether neuroinflammation and soluble A¦Â production are associated with A¦Â plaque and hyperphosphorylated tau deposition in the brain. Male Sprague Dawley rats received a single intraperitoneal injection of 10 mg/kg of lipopolysaccharide endotoxin (LPS). Brain and blood levels of IL-1¦Â, IL-6, and TNF¦Á and cortical microglial density were measured in LPS-injected and control animals. Soluble brain A¦Â and p-tau were compared and A¦Â plaques were quantified and characterized. Brain uptake of [18F]flutemetamol was measured by phosphor imaging. LPS endotoxemia resulted in elevations of cytokines in blood and brain. Microglial density was increased in LPS-treated rats relative to controls. LPS resulted in increased soluble A¦Â and in p-tau levels in whole brain. Progressive increases in morphologically-diffuse A¦Â plaques occurred throughout the interval of observation (to 7-9 days post LPS). LPS endotoxemia resulted in increased [18F]flutemetamol in the cortex and increased cortex: white matter ratios of activity. In conclusion, LPS endotoxemia causes neuroinflammation, increased soluble A¦Â and A¦Â diffuse plaques in the brain. A¦Â PET tracers may inform this neuropathology. Increased p-tau in the brain of LPS treated animals suggests that downstream consequences of A¦Â plaque formation may occur. Further mechanistic and neurocognitive studies to understand the causes and consequences of LPS-induced neuropathology are warranted
%K Lipopolysaccharide
%K LPS
%K sepsis
%K neuroinflammation
%K amyloid beta
%K phosphorylated tau
%K brain
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944824/