Amyloid biomarkers in Alzheimer's disease

•Amyloid-β (Aβ) aggregation is central in Alzheimer disease the molecular pathogenesis. •The biomarkers amyloid PET and CSF Aβ42 are available to monitor Aβ pathology. •Amyloid PET and CSF Aβ42 show high concordance and similar diagnostic accuracy. •Standardization efforts are needed for both amyloid PET and CSF Aβ42. Aggregation of amyloid-β (Aβ) 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 Aβ metabolism and aggregation directly in patients are important for further detailed study of the involvement of Aβ in disease pathogenesis and to monitor the biochemical effect of drugs targeting Aβ in clinical trials. Furthermore, if anti-Aβ 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 Aβ metabolism or pathology to guide dosage. Two types of amyloid biomarker have been developed: Aβ-binding ligands for use in positron emission tomography (PET) and assays to measure Aβ42 in cerebrospinal fluid (CSF). In this review, we present the rationales behind these biomarkers and compare their ability to measure Aβ 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. Aggregation of amyloid-β (Aβ) 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 Aβ metabolism and aggregation directly in patients are important for further detailed study of the involvement of Aβ in disease pathogenesis and to monitor the biochemical effect of drugs targeting Aβ in clinical trials. Furthermore, if anti-Aβ 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 Aβ metabolism or pathology to guide dosage. Two types of amyloid biomarker have been developed: Aβ-binding ligands for use in positron emission tomography (PET) and assays to measure Aβ42 in cerebrospinal fluid (CSF). In this review, we present the rationales behind these biomarkers and compare their ability to measure Aβ 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.