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Novel tracers for PET imaging and the increasing range of CSF and plasma assays for amyloid-β and tau are steps on the way to routine use of diagnostic biomarkers in Alzheimer’s dementia (AD). A strategic roadmap is systematically monitoring the advance of each marker towards eventual clinical utility.
The advent of reliable fully automated assays for amyloid-β in CSF1 and efforts to standardize the handling of samples before measurement are among the most important recent developments in the search for fluid biomarkers, Antoine Leuzy (University of Lund, Sweden) told the AAIC2020 session. Steps towards a unified protocol for sample collection, storage and dealing with blood contamination have been proposed.2
Task Force roadmap tells us how far each marker has come and how far it still has to go
In relation to plasma markers, we now have early evidence that P-tau181 in blood is highly sensitive and highly specific in differentiating AD from other neurodegenerative disorders, he said.
Tracking the tracers
Compared with earlier agents, second-generation tau PET tracers offer significantly reduced off-target binding, reported Gérard Bischof (University of Köln, Germany). Pharmacokinetics are also good.3 Their clinical validation is under way, and a recent study of one second-generation tracer -- involving patients in the Swedish BioFINDER-2 trial -- showed encouragingly high specificity for AD-related tau and hence good potential as a diagnostic marker in differential diagnosis.4
Completing the clinical validation of these novel compounds requires standardization and aggregation of larger datasets. As for evaluating clinical utility, this will depend on the availability of the relevant compounds and the necessary on-site infrastructure, Dr Bischof said.
We need to know where we are going before we can say we’ve arrived
Tau markers included in standardized roadmap
When faced with so many potential markers, a comprehensive framework to standardize their evaluation is as important as the markers themselves. Hence the current focus of the Geneva-based international task force on a strategic roadmap adapted from an approach used in oncology.5 This AD framework now includes tau markers, which were not considered in the 2017 strategy.
For each marker, progress involves the sequential demonstration of:
Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.
1. Bittner T et al. Alzheimers Dement 2016;12:517-26
2. Janelidze S et al. Alzheimer's Research and Therapy 2019;11: 63
3. Gobbi TC et al. J Medicinal Chem 2017; J Med Chem 2017;60:7350-70
4. Leuzy A et al. JAMA Neurol May 11 2020
5. Frisoni GB et al. Lancet Neurology 2017;16:661-76