Comparing 18 F-AV-1451 with CSF t-tau and p-tau for diagnosis of Alzheimer disease

Objective To compare PET imaging of tau pathology with CSF measurements (total tau [t-tau] and phosphorylated tau [p-tau]) in terms of diagnostic performance for Alzheimer disease (AD). Methods We compared t-tau and p-tau and 18 F-AV-1451 in 30 controls, 14 patients with prodromal AD, and 39 patients with Alzheimer dementia, recruited from the Swedish BioFINDER study. All patients with AD (prodromal and dementia) were screened for amyloid positivity using CSF β-amyloid 42. Retention of 18 F-AV-1451 was measured in a priori specified regions, selected for known associations with tau pathology in AD. Results Retention of 18 F-AV-1451 was markedly elevated in Alzheimer dementia and moderately elevated in prodromal AD. CSF t-tau and p-tau was increased to similar levels in both AD dementia and prodromal AD. 18 F-AV-1451 had very good diagnostic performance for Alzheimer dementia (area under the receiver operating characteristic curve [AUROC] ∼1.000), and was significantly better than t-tau (0.876), p-tau (0.890), hippocampal volume (0.824), and temporal cortical thickness (0.860). For prodromal AD, there were no significant AUROC differences between CSF tau and 18 F-AV-1451 measures (0.836-0.939), but MRI measures had lower AUROCs (0.652-0.769). Conclusions CSF tau and 18 F-AV-1451 have equal performance in early clinical stages of AD, but 18 F-AV-1451 is superior in the dementia stage, and exhibits close to perfect diagnostic performance for mild to moderate AD. Classification of evidence This study provides Class III evidence that CSF tau and 18 F-AV-1451 PET have similar performance in identifying early AD, and that 18 F-AV-1451 PET is superior to CSF tau in identifying mild to moderate AD.