Revolutionizing Alzheimer's disease and clinical trials through biomarkers

Abstract

The Alzheimer's Association's Research Roundtable met in May 2014 to explore recent progress in developing biomarkers to improve understanding of disease pathogenesis and expedite drug development. Although existing biomarkers have proved extremely useful for enrichment of subjects in clinical trials, there is a clear need to develop novel biomarkers that are minimally invasive and that more broadly characterize underlying pathogenic mechanisms, including neurodegeneration, neuroinflammation, and synaptic dysfunction. These may include blood-based assays and new neuropsychological testing protocols, as well as novel ligands for positron emission tomography imaging, and advanced magnetic resonance imaging methodologies. In addition, there is a need for biomarkers that can serve as theragnostic markers of response to treatment. Standardization remains a challenge, although international consortia have made substantial progress in this area and provide lessons for future standardization efforts.

Blood‐based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic

“…Therefore, there has been a significant interest in predictive and response biomarkers. Blood-based biomarkers may have utility to provide a cost-effective means for the identification of predictive biomarkers that identify specific subsets of patients most likely to respond to a given therapy[2, 62], which is a key focus of blood-based (genetic, proteomic and other) markers in the precision medicine approach to cancer therapy (e.g. EGFR in predicting response to non-small cell lung cancer, BRCA1/2 mutations in predicting response among women with ovarian cancer).…”

Plasma tau in Alzheimer disease

“…1 These technologies have revolutionized clinical research and trials and are rapidly transforming clinical practice. 2 However, they are hampered by their relative invasiveness and high costs. There is a great unmet need for less invasive and cheaper biomarkers of AD pathology.…”

An amylin analog used as a challenge test for Alzheimer's disease

“…Because RBP-4 is linked with insulin resistance in the brain and is increased in the brain of AD mouse models [31], these data might reveal the AD pathology in the brain as the change in RBP-4 could be a useful biomarker for AD. As neuroinflammation is a key, but not specific, component of AD pathology in the brain, especially at a late stage of the disease [44,45], our findings showed that the pramlintide challenge increased IL-1Ra in AD but not in MCI (Fig. 5).…”