Development of novel therapies for Alzheimer’s Disease (AD) is constrained by the lack of available methods for preclinical diagnosis, despite extensive research on biomarker identification. The EMPIR NeuroMET project unites National Measurement Laboratories, clinicians and academics, to overcome limitations in measurement methods and provide a better understanding of how to improve, combine and analyse measurements in AD diagnosis and treatment. Comparability through SI (System of International Units) traceability and uncertainty analysis is an, as yet, unmet requirement for regulatory approval of biomarkers, patient centred outcome measures, clinical thresholds and new therapeutic drugs. We will report on:

• Multimodal statistical analysis on blood, CSF and saliva biomarkers data from the NeuroMET cohort generated by using mass spectroscopy and immunoassay platforms, including a novel immunoassay approach to overcome matrix effects when relative quantification is not sensitive enough. A new digital PCR approach was developed to assess microRNAs quantities in blood to compare with established biomarkers.
• Progress towards the development of mass spectrometry reference measurement procedures traceable to the SI for t-tau and α-synuclein in cerebrospinal fluids.
• Development of ultrahigh field Magnetic Resonance Imaging and Spectroscopy protocols for increased spatial and spectral resolution and decreased uncertainty, and their application to the NeuroMET cohort.
• Improved cognitive assessment protocols, with improved metrological evaluation of cognitive performance scores and the development of construct specification equations for various cognitive protocols and biomarkers.
• Potential relationships between volumes of AD-related brain structures and neurometabolite concentrations with measured cognitive function.

Improved reference methods to underpin the production of calibrators and improve measurement comparability of established biomarkers has the potential to further the understanding of AD and boost research for disease modifying therapies.