Blood-based biomarkers for Alzheimer disease: mapping the road to the clinic. Issue 11 (November 2018) - Hampel, Harald
Abstract Biomarker discovery and development for clinical research, diagnostics and therapy monitoring in clinical trials have advanced rapidly in key areas of medicine — most notably, oncology and cardiovascular diseases — allowing rapid early detection and supporting the evolution of biomarker-guided, precision-medicine-based targeted therapies. In Alzheimer disease (AD), breakthroughs in biomarker identification and validation include cerebrospinal fluid and PET markers of amyloid-β and tau proteins, which are highly accurate in detecting the presence of AD-associated pathophysiological and neuropathological changes. However, the high cost, insufficient accessibility and/or invasiveness of these assays limit their use as viable first-line tools for detecting patterns of pathophysiology. Therefore, a multistage, tiered approach is needed, prioritizing development of an initial screen to exclude from these tests the high numbers of people with cognitive deficits who do not demonstrate evidence of underlying AD pathophysiology. This Review summarizes the efforts of an international working group that aimed to survey the current landscape of blood-based AD biomarkers and outlines operational steps for an effective academic–industry co-development pathway from identification and assay development to validation for clinical use. Advances in biomarker research are aiding the development of targeted therapies and prevention strategies for Alzheimer disease (AD). In this Review, an international working group assesses the current status of blood-based AD biomarkers and outlines a roadmap for future research. Key points Cerebrospinal fluid (CSF) and PET markers of amyloid-β and tau proteins are accurate in detecting the neuropathological changes of Alzheimer disease (AD). The use of CSF and PET biomarkers is limited by invasiveness or high costs; to address these issues, blood-based AD biomarkers are eagerly awaited. An international, interdisciplinary expert working group was convened by the Alzheimer's Precision Medicine Initiative to discuss the ideal development process for blood-based biomarkers. Nineteen blood-based biomarker assays were selected by the working group for further consideration. The working group outlined the pathway from biomarker identification and assay development to validation for clinical use and proposed clear steps for effective academic–industry co-development of blood-based AD biomarkers. The development, standardization and validation of blood-based biomarkers will be paramount to the implementation of precision medicine in AD.