Blood-based biomarkers for Alzheimer's disease

Neurodegenerative disorders such as Alzheimer's disease (AD) represent a mounting public health challenge. As these diseases are difficult to diagnose clinically, biomarkers of underlying pathophysiology are playing an ever-increasing role in research, clinical trials, and in the clinical work-up of patients. Though cerebrospinal fluid (CSF) and positron emission tomography (PET)-based measures are available, their use is not widespread due to limitations, including high costs and perceived invasiveness. As a result of rapid advances in the development of ultra-sensitive assays, the levels of pathological brain- and AD-related proteins can now be measured in blood, with recent work showing promising results. Plasma P-tau appears to be the best candidate marker during symptomatic AD (i.e., prodromal AD and AD dementia) and preclinical AD when combined with A beta 42/A beta 40. Though not AD-specific, blood NfL appears promising for the detection of neurodegeneration and could potentially be used to detect the effects of diseasemodifying therapies. This review provides an overview of the progress achieved thus far using AD blood-based biomarkers, highlighting key areas of application and unmet challenges.