Alzheimer's disease biomarker analysis using targeted mass spectrometry

Alzheimer’s disease (AD) is characterised by several neuropathological changes, mainly extracellular amyloid aggregates (plaques), intraneuronal inclusions of phosphorylated tau (tangles), as well as neuronal and synaptic degeneration, accompanied by tissue reactions to these processes (astrocytosis and microglial activation) that precede neuronal network disturbances in the symptomatic phase of the disease. A number of biomarkers for these brain tissue changes have been developed, mainly using immunoassays. In this review, we discuss how targeted mass spectrometry (TMS) can be used to validate and further characterize classes of biomarkers reflecting different AD pathologies, such as tau- and amyloid-beta pathologies, synaptic dysfunction, lysosomal dysregulation, and axonal damage, and the prospect of using TMS to measure these proteins in clinical research and diagnosis. TMS advantages and disadvantages in relation to immunoassays are discussed, and complementary aspects of the technologies are discussed.