AAIC 2023 | Time gap between amyloid- and tau-PET positivity in preclinical disease

This was basically a longitudinal study in which we applied some mathematical modeling to estimate the time between the two hallmarks in Alzheimer’s disease, which is the presence of amyloid pathology and then the presence of advanced tau pathology. So we measured this with PET, which is the only biomarker modality in which we can directly measure the presence of amyloid pathology and the presence of neurofibrillary tangles, the presence of tau pathology, and we estimated this time gap. It’s about nine years between once you enter the Alzheimer’s continuum, once you become amyloid positive, the median survival time without tau pathology is about nine years. So we also analyzed the potential implications for Alzheimer’s disease prevention trials, trials testing therapies at the prevention stage, therapies applied when you have no cognitive symptoms at all and we basically found something quite interesting, which is that after 77 years of age, the majority of participants who are amyloid-positive but tau-negative, that is, they are in the Alzheimer’s continuum, but they don’t have a complete biomarker profile consistent with Alzheimer’s disease, the majority of these individuals, will never develop a tau positivity, which is which is necessary to develop cognitive symptoms due to Alzheimer’s disease. So, yeah, that was our main conclusion. We might need to select appropriate candidates, not only identified those candidates who are amyloid-positive, but we probably need to select those candidates who are also tau-positive, right? So that was the main message of our study. We need to provide a more fine-grained staging of progression based on biomarkers and in particular on tau-PET.