LAUSR

Biomarkers can be regarded as highly objective, quantifiable, and reproducible medical signs, that is, “objective indications of medical state observed from outside the patientdin contrast to medical symptoms, which are perceived by patients themselves” (Strimbu and Tavel, 2010). Advances in omics technology led to a boom in biomarker research (Ghosh and Poisson, 2009). A PubMed search of the word “biomarker*” in the title of medical articles gives back 7 entries in 1985, 117 in 1995, 946 in 2005, and 6448 in 2015. Seventeen scientific journals carry the word “biomarker” in their name, half launched in the past 5 years. Most biomarker research is in oncology. However, even here the gap is striking between the bulk of biomarker research and the few biomarkers that find their way into the clinic (Füzéry et al., 2013). Perhaps, the major reason for the discrepancy is the poorly structured and regulated environment of biomarker development, validation, and clinical uptake. The US Food and Drug Administration closely inspects laboratory techniques and equipment but generally does not ascertain the validity of the particular tests the laboratories deploy (Editorial, 2014a). Yet, the potential gain from the clinical use of valid biomarkers for diagnosis, disease tracking, or drug development is huge. The Alzheimer’s field is no exception. Biomarker-based diagnostic criteria allowing earlier and more accurate etiologic diagnosis have been developed (IWG and NIA-AA) that make use of hippocampal atrophy on magnetic resonance, cortical hypometabolism on 18F fludeoxyglucose-positron emission tomography (FDG-PET), decreased amyloid-b 42 and increased tau and phospho-tau in the cerebrospinal fluid (CSF), and increased uptake of amyloid ligands on PET (Dubois et al., 2014; Jack et al., 2011). Despite advice to the contrary (Frisoni et al., 2011), these are currently used in the clinic, but personal experience indicates that clinicians’ use may be based more on nonclinical factors (e.g., availability of and familiarity with the biomarker, length of the waiting list, and so forth) than clinical factors (e.g., severity of cognitive impairment, suspicion of cerebrovascular disease, and so forth), as has been shown for the clinical use of diagnostic imaging technology (Frisoni et al., 2005; Riello et al., 2003). As a consequence of the concern that the current scenario is not in the patients’ best interest, a number of clinical scientists have joined in an initiative to develop a structured agenda (i.e., a roadmap) aiming to accelerate the rational integration of Alzheimer’s disease (AD) biomarkers into the clinic. The first step we took was a workshop in Cernobbio (Italy) on November 12, 2012 under the auspices of the Italian Ministry of Health where representatives of the pertinent Italian scientific societies took part (nuclear medicine, neuroradiology, clinical biochemistry, clinical molecular biology, neuropsychology, neurology, and psychogeriatrics). The article by