Alzheimer`s disease (AD) is the most common form of dementia, caused predominantly by amyloid plaques, consisting of insoluble fibrils of aggregated amyloid beta (A?) peptides. Structural information on early aggregation products of these peptides is limited. Recently, modern mass spectrometric (MS) techniques, especially electrospray ionization (ESI), have been introduced in several A? studies and have yielded promising results. ESI is a soft ionization technique and allows detection of signals from all co-existing stabile ionized molecular species in solution. Moreover, charge-state distribution in ESI MS spectra provides information about conformational state of proteins/peptides, which is very useful for detection of environment-induced conformational changes in protein/peptide structure. The potential of ESI MS technique and its compatibility with liquid chromatography (LC) for determination of oligomers of amyloidogenic peptides has not been exploited in full scale. Therefore, within proposed project, we will use LC/MS and ESI MS to study the conformation, oligomerization and aggregation of amyloidogenic peptides in different environmental conditions. Main emphasis will be put on development and application of innovative methods employing ESI MS, and coupling LC and MS for detection of oligomers and early aggregates in A? fibrillization.