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

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