F-AV-1451 and CSF T-tau and P-tau as biomarkers in Alzheimer’s disease

To elucidate the relationship between cerebrospinal fluid (CSF) total-tau (T-tau) and phosphorylated tau (P-tau) with the tau PET ligand F-AV-1451 in Alzheimer’s disease (AD), we examined 30 cognitively healthy elderly (15 with preclinical AD), 14 prodromal AD, and 39 AD dementia patients. CSF T-tau and P-tau were highly correlated (R = 0.92, P < 0.001), but they were only moderately associated with retention of F-AV-1451, and mainly in demented AD patients. F-AV-1451, but not CSF T-tau or P-tau, was strongly associated with atrophy and cognitive impairment. CSF tau was increased in preclinical AD, despite normal F-AV-1451 retention. However, not all dementia AD patients exhibited increased CSF tau, even though F-AV-1451 retention was always increased at this disease stage. We conclude that CSF T-tau and P-tau mainly behave as biomarkers of “disease state”, since they appear to be increased in many cases of AD at all disease stages, already before the emergence of tau aggregates. In contrast, F-AV-1451 is a biomarker of “disease stage”, since it is increased in clinical stages of the disease, and is associated with brain atrophy and cognitive decline.