AD biomarker discovery in CSF and in alternative matrices.

Core Alzheimer's Disease (AD) biomarkers are the cerebrospinal fluid (CSF) proteins amyloid β42 and β40, and the tau proteins, total and phosphorylated. Their use is recommended by research guidelines for diagnostic purpose and for stratification of patients for clinical trials. However, novel potential biomarkers are needed, which can mirror risk factors and other different mechanisms of the disease, hopefully in less invasive biological fluids or matrices. Studies on blood, urine, saliva, tears gave promising results, and several novel molecules have been identified, as potential brain derived biomarkers, thanks to the development of novel ultrasensitive technologies. In this review, we discuss about advantages and limits of the classical CSF biomarkers of AD, as well as of novel CSF candidate biomarkers and recent promises from alternative matrices.