While blood-based tests are readily available for various conditions, including cardiovascular diseases, type 2 diabetes, and common cancers, Alzheimer's disease (AD) and other neurodegenerative diseases lack an early blood-based screening test that can be used in primary care. Major efforts have been made towards the investigation of approaches that may lead to minimally invasive, cost-effective, and reliable tests capable of measuring brain pathological status. Here, we review past and current technologies developed to investigate biomarkers of AD, including novel blood-based approaches and the more established cerebrospinal fluid and neuroimaging biomarkers of disease. The utility of blood as a source of AD-related biomarkers in both clinical practice and interventional trials is discussed, supported by a comprehensive list of clinical trials for AD drugs and interventions that list biomarkers as primary or secondary endpoints. We highlight that identifying individuals in early preclinical AD using blood-based biomarkers will improve clinical trials and the optimization of therapeutic treatments as they become available. Lastly, we discuss challenges that remain in the field and address new approaches being developed, such as the examination of cargo packaged within extracellular vesicles of neuronal origin isolated from peripheral blood.
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