Detection, diagnosis, and monitoring of Alzheimer's disease can be achieved with antibody-based detection methods directed to detect at least two regions of the amyloid beta peptide. The invention recognizes and relies on the observation that the steric availability of the carboxyl terminal epitope and the amino terminal epitope in an amyloid beta peptide differs based on whether the amyloid beta is monomeric or oligomeric. Due to oligomerization, the measured concentration of carboxyl termini that are available for binding represents the amount of monomeric amyloid beta in the sample; whereas the measured concentration of amino termini that are available for binding represents total amyloid beta (i.e., monomeric plus oligomeric) in the sample. Comparing the relative binding therefore can be used to characterize the population of soluble amyloid beta oligomers in the sample. The measurements are useful for early detection and subsequent monitoring of the development of Alzheimer's disease in a patient.