Amyloid biomarkers in Alzheimer's disease

Aggregation of amyloid-beta (A beta) into oligomers, fibrils, and plaques is central in the molecular pathogenesis of Alzheimer's disease (AD), and is the main focus of AD drug development. Biomarkers to monitor A beta metabolism and aggregation directly in patients are important for further detailed study of the involvement of A beta in disease pathogenesis and to monitor the biochemical effect of drugs targeting A beta in clinical trials. Furthermore, if anti-A beta disease-modifying drugs prove to be effective clinically, amyloid biomarkers will be of special value in the clinic to identify patients with brain amyloid deposition at risk for progression to AD dementia, to enable initiation of treatment before neurodegeneration is too severe, and to monitor drug effects on A beta metabolism or pathology to guide dosage. Two types of amyloid biomarker have been developed: A beta-binding ligands for use in positron emission tomography (PET) and assays to measure A beta 42 in cerebrospinal fluid (CSF). In this review, we present the rationales behind these biomarkers and compare their ability to measure A beta plaque load in the brain. We also review possible shortcomings and the need of standardization of both biomarkers, as well as their implementation in the clinic.