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Cerebrospinal fluid (CSF) biomarkers are routinely used to diagnose Alzheimer's disease (AD), as outlined by Alberto Lleó, MD, PhD, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Initially, ELISAs were used to detect biomarkers, however, the availability of automatic platforms has resulted in more accurate results with minimal variability, leading to their widespread use in clinics. Dr Lleó talks on the 10-year experience with CSF biomarkers conducted at his center, which aimed to optimize markers for disease detection in very early stages. It was shown that better results were obtained by identifying four key biomarkers: β-amyloid peptide 42 (Aβ42), Aβ40, total tau and phosphorylated tau levels, instead of only three biomarkers as in earlier assays. It is also important to ensure widespread quality control in the detection of biomarkers across different centers for AD diagnosis, with the introduction of universal cut-offs. This interview took place at the Harvard European Alumni Training Network (HEAT-Net) 2021 congress.