Mass spectrometry is a multifaceted weapon to be used in the battle against Alzheimer's disease: Amyloid beta peptides and beyond.

Amyloid-β peptide (Aβ) accumulation and aggregation have been considered for many years the main cause of Alzheimer's disease (AD), and therefore have been the principal target of investigation as well as of the proposed therapeutic approaches (Grasso [2011] Mass Spectrom Rev. 30: 347-365). However, the amyloid cascade hypothesis, which considers Aβ accumulation the only causative agent of the disease, has proven to be incomplete if not wrong. In recent years, actors such as metal ions, oxidative stress, and other cofactors have been proposed as possible co-agents or, in some cases, main causative factors of AD. In this scenario, MS investigation has proven to be fundamental to design possible diagnostic strategies of this elusive disease, as well as to understand the biomolecular mechanisms involved, in the attempt to find a possible therapeutic solution. We review the current applications of MS in the search for possible Aβ biomarkers of AD to help the diagnosis of the disease. Recent examples of the important contributions that MS has given to prove or build theories on the molecular pathways involved with such terrible disease are also reviewed.