Key Alzheimer’s disease (AD) brain changes are clumping of the proteins amyloid and tau into plaques and tangles, which cause degeneration and loss of neurons that result in progressive memory loss and cognitive symptoms. Both spinal fluid (CSF) and PET tests for amyloid and tau pathology are available, but these are either invasive (CSF tests) or have high costs and insufficient accessibility (PET), which limit their use as first-in-line biomarker tools.

      Specifically, the lack of blood biomarkers for tau pathology and neuronal injury constitutes a major barrier to the effective read-out of results on these pathologies in clinical trials. Indeed, while anti-amyloid immunotherapy have shown very promising results with reductions in brain amyloidosis, no data are available on whether this is accompanied by reduced tau pathology and neurodegeneration.

      This project builds on the identification of development of sensitive and specific blood tests for neurodegeneration and tau pathology. It relies on the fundamental principle that only a fraction of tau molecules in plasma originates from the brain. Therefore, assay development, including antibody generation, will be guided by mass spectrometry-based characterization of tau in plasma, detecting specific tau forms that are brain-enriched; only blood tau assays that show a sharp correlation with brain pathology will be taken forward. We already have identified some highly promising candidates, and will apply our established workflow for biomarker development, accompanied by a thorough validation of the assays.

      We envision that blood tests for tau pathology and neurodegeneration would be a major breakthrough in the arsenal of tools available in the primary care setting for evaluation of patients for possible inclusion in clinical trials, and to monitor the effects of anti-AD drugs in future clinical practice the day we have disease-modifying treatments.