The immunodetection of lipoprotein-bound amyloid-beta is attenuated because of the presence of lipids

Background Amyloid-beta (Abeta) is found in circulation and cerebrospinal fluid (CSF), predominantly associated with lipoproteins. However, in a lipid environment it is possible that a masking of Abeta epitopes and/or an altered conformation of Abeta leads to an underestimation of Abeta concentrations. Methods We generated lipoprotein-like lipid emulsions containing a known amount of Abeta and compared immunoreactivity with an equimolar amount of Abeta solubilized in an aqueous medium. Results We found that Abeta exists primarily as a dimer and a monomer within an aqueous and lipid environment, respectively. We also showed that lipids bind tightly to Abeta, blocking detection of the monomeric form and substantially attenuating detection of the dimeric form of the protein. Conclusion It is possible that studies that have quantified the concentration of Abeta in plasma and CSF may have significantly underestimated the pool of lipoprotein-bound Abeta.