Aβ42 is a 42 amino acid proteolytic product from the amyloid precursor protein that has gained considerable attention as a biomarker correlating with Alzheimer disease (AD) onset, mild cognitive impairment, vascular dementia, and other cognitive disorders. Amyloid beta (Aβ) peptides (including the shorter Aβ38 and Aβ40 isoforms) are produced by many cell types in the body but the expression is particularly high in the brain. Accumulation of Aβ in the form of extracellular plaques is a neuropathological hallmark of AD and thought to play a central role in the neurodegenerative process. Substantial clinical validation has now been developed around disease relevance of cerebrospinal fluid (CSF) levels of Aβ42, and there follows a significant interest in measuring blood levels of this marker. Concentrations of Aβ42 in blood are over 100-fold lower than in cerebrospinal fluid, (typically single pg/mL range), requiring very high analytical sensitivity for its reliable measurement.