Innate immune signaling in Alzheimer's disease pathogenesis
Dr. Kathryn Moore and colleagues identified a trigger mechanism common to both atherosclerosis and Alzheimer's disease that involves the activation of the innate immune response. The innate immune response provides an immediate, but not long-lasting, defense against infection. Three cell surface proteins, called TLR4, TLR6 and CD36, normally recognize specific protein patterns found on microbes to activate the immune system to destroy the foreign invaders. In this research grant, Dr. Moore discovered that these three proteins can also assemble into a newly-identified complex that recognizes both Alzheimer's-associated beta-amyloid and the atherosclerosis-associated protein oxidized LDL. This interaction further induces inflammation signals that may promote the development of these two diseases. Dr. Moore has identified a common pathway involved in triggering and maintaining inflammation in atherosclerosis and Alzheimer's disease. These findings present exciting opportunities to treat both of these aging diseases by creating new therapies targeting TLR4, TLR6 and CD36.
(This study identifies an innate immune signaling complex composed of CD36 and a novel Toll-like receptor (TLR) heterodimer of TLR4 and TLR6 that mediates the inflammatory response to atherogenic LDL and -amyloid, including the neurotoxicity that is pathogenomonic of Alzheimer's disease. This work identifies a common molecular mechanism underlying innate immune activation in atherosclerosis and Alzheimer disease. This was featured in a press release from Nature Immunology and highlighted in Nature Reviews in Immunology.)
First published on: Tuesday, June 10, 2008
Last modified on: Tuesday, April 12, 2011