Amyloid plaques are found in postmortem Alzheimer’s disease (AD) patients’ brains and their major components are amyloid-b peptides(Ab). Ab is a key component of the biochemical process of AD pathogenesis; therefore, it is studied as biomarker for diagnosis.. Cerebrospinal fluid (CSF) is in direct contact with the brain and it is the most meaningful source of biomarkers for neurodegenerationand also of Ab peptide concentration monitoring. Due to difficulties and side effects of CSF drawn, plasma is used as body fluid for ADbiomarker studies.. Ab peptides are notoriously hydrophobic, they bind to biomolecules and they are produced by several organs in human body; theirpresence in blood is related to several biological processes, therefore, their identification/quantification in plasma is challenging.. Plasma Ab does not correlate to AD diagnosis or progression but it might be useful to monitor amyloid response for disease progressionin drug targeting studies or drug treatment.. Ab concentrations in AD and healthy control subjects measured by ELISA show huge inter-laboratory differences. Antibody masking, Aboligomerization and complex formation make ELISA measurements less reproducible in inter-laboratory studies. A quantification methodable to give an accurate absolute concentration value is needed.. Mass spectrometry-based methods (like selected reaction monitoring) seem to be the best alternative to ELISA, able to give areproducible quantification.. Low endogenous Ab need an enrichment prior to mass spectrometry-based quantification; immunoprecipitation and solid phaseextraction are the most used and promising techniques.