The LPS receptor (CD14) links innate immunity with Alzheimer's disease

Abstract

SPECIFIC AIMIn Alzheimer’s disease (AD), chronic neuroinflammation induced by amyloid peptide (Aβ) fibrils is considered to contribute to progressive neurodegeneration. We studied whether the LPS receptor (CD14), crucial in cellular activation by highly hydrophobic and aggregated microbial components, mediates inflammatory activation by hydrophobic aggregated Aβ and whether this key innate immunity receptor is associated with pathological features in a mouse model of AD.PRINCIPAL FINDINGS1. CD14 interacts with Aβ fibrilsTo determine whether CD14 binds Alzheimer Aβ, we coincubated fibrillar human Aβ(1-42) with recombinant soluble murine CD14. Complexes were immunoprecipitated and assessed by Western blot. The results demonstrate binding of Aβ fibrils to CD14. Omission of Aβ or use of an isotype control antibody prevented the precipitation of CD14. Coincubation with the control peptide TNF-α receptor II instead of CD14 did not result in a coimmunoprecipitation as indicated by the absence of a corresponding ...