The Alzheimer's Association appropriate use recommendations for blood biomarkers in Alzheimer's disease

Abstract

Blood-based markers (BBMs) have recently shown promise to revolutionize the diagnostic and prognostic work-up of Alzheimer's disease (AD), as well as to improve the design of interventional trials. Here we discuss in detail further research needed to be performed before widespread use of BBMs. We already now recommend use of BBMs as (pre-)screeners to identify individuals likely to have AD pathological changes for inclusion in trials evaluating disease-modifying therapies, provided the AD status is confirmed with positron emission tomography (PET) or cerebrospinal fluid (CSF) testing. We also encourage studying longitudinal BBM changes in ongoing as well as future interventional trials. However, BBMs should not yet be used as primary endpoints in pivotal trials. Further, we recommend to cautiously start using BBMs in specialized memory clinics as part of the diagnostic work-up of patients with cognitive symptoms and the results should be confirmed whenever possible with CSF or PET. Additional data are needed before use of BBMs as stand-alone diagnostic AD markers, or before considering use in primary care.

Keywords: Alzheimer's disease; appropriate use recommendations; blood-based biomarkers; diagnosis; prognosis.

FIGURE 1

Potential future use of blood‐based biomarkers in clinical trials. Biomarker applications in clinical trials for Alzheimer's disease (AD) can be useful for screening, inclusion, and treatment outcomes. The various purposes of each type are indicated in the columns. Screening and inclusion: Clinical trials depend on correct grouping of subjects for the right treatments, therefore various biomarkers and inclusion criteria can be used. Categorization of subjects can be done using risk/susceptibility biomarkers (indicate the potential for developing the disease), diagnostic biomarkers (detect or confirm the presence of a disease), stratification markers (such as age or genetic risk factors, for example apolipoprotein E ε4, for which strata are expected to have a stronger response to treatment), and predictive biomarkers (determine who might benefit from and respond to a particular treatment). Treatment outcomes: Once the clinical trials have begun, response and outcomes for the subjects can be monitored by measuring the effects on the target protein of the drug as well by biomarkers as endpoints of the clinical trials; the holy grail is to use biomarkers as surrogate endpoints that predict the clinical endpoints

FIGURE 2

Potential future use of blood‐based biomarkers in primary care. In primary care we need easy and accurate methods to be able to identify different underlying neurodegenerative diseases in patients with cognitive complaints. Ideally blood‐based biomarkers together with clinical assessments could be used to determine the patient‐level probability of having a neurodegenerative disease like Alzheimer's disease (AD), which would improve patient management, including decisions regarding treatment or referrals to specialized clinics. However, it is very important that novel diagnostic algorithms (based on blood‐based biomarkers) are prospectively validated against relevant reference standards in large and diverse primary care populations before implementation in clinical practice