Abstract Body

Recent studies showing that it is possible to accurately detect the core AD pathologies amyloid deposition (A), tau pathology (T), and neurodegeneration (N), using easily accessible blood tests.

For A, ultrasensitive immunoassays and immunoprecipitation - mass spectrometry (IP-MS) methods show very high concordance (up to >90%) with brain amyloidosis evaluated by PET. For T, several phosphorylated tau species (P-tau181, P-tau217) in blood, show a specific increase in AD, and high concordance with tau PET. Further, plasma P-tau is increased very early, in cognitively unimpaired elderly who have a positive amyloid PET scan. For N, blood NFL reflects axonal degeneratio, with plasma levels being increased even in early stages of the disease, but also tracks neurodegeneration during the AD continuum. These biomarkers also show very low variation in longitudinal samples, and thus promise as a tool to monitor drug therapies, but we are still awaiting data on how these blood biomarkers perform in clinical trials on drugs showing clinical benefit.

Further work is needed to standardize these assays for clinical use, especially the development of Certified Reference Measurement Procedures (“Gold Standard methods”) and Certified Reference Materials (aliquoted plasma pools with known biomarker levels) to assure batch-to-batch stability and for harmonization across assays. We also need studies validating the diagnostic performance in prospective studies using pre-set cut-offs, with samples analysed week by week as they come to the lab.

These blood biomarkers show promise for being clinically useful, easily accessible and cheap, tools for screening and possibly also diagnostics.