Amyloid-beta (Abeta) peptide levels are widely measured by enzyme-linked immunosorbent assay (ELISA) in Alzheimer's disease research. Here, we show that oligomerization of Abeta results in underestimated Abeta ELISA levels. The implications are that comprehensive analysis of soluble Abeta requires either sample pretreatment at denaturing conditions or novel conformation-dependent immunoassays. Our findings might be of relevance for many neurodegenerative disorders in which soluble protein aggregates are the main neurotoxic species.