Longitudinal cerebrospinal fluid phosphorylated tau181 and total tau do not reflect tau PET retention in dominantly inherited Alzheimer disease

Background Although Alzheimer disease (AD) related changes of tau can be measured in fluids and by positron emission tomography (PET), it remains unclear how these two are associated across the AD spectrum. To further explore the association between soluble tau related biomarkers‐ cerebrospinal fluid (CSF) total tau and p‐tau181‐ and neurofibrillary tangles (NFT) (flortaucipir PET), we compared longitudinal change of each in the dominantly inherited AD trials unit (DIAN‐TU) trial of solanezumab and gantenerumab. Method 73 Mutation carriers (MC) (31 CDR>0) from the DIAN‐TU‐001 study (30 gantenerumab, 20 solanezumab, 23 shared placebo) underwent longitudinal collection of CSF for measurement of p‐tau181 and total tau, and flortaucipir tau PET over 2.3 (0.92) mean (SD) years; tau PET was available at baseline for 26% of participants. Individual rates of change for CSF measures and tau PET retention were estimated using the method of least squares. Spearman correlations of the rate of change were used to assess the association between CSF and tau PET. Result For all MCs the change of CSF p‐tau181 and tau had no association with change in tau PET standard uptake value ratio SUVR (r = 0.01, p‐0.95 and r = 0.10, p‐0.43), figure . When limiting the correlations to those in the gantenerumab arm, where a significant reduction in p‐tau181 and total tau was previously identified, there remained no clear association between a reduction in soluble tau measures in CSF and change in tau PET SUVR (r=‐0.21, p‐0.27 and r= ‐0.08, p‐0.71). Conclusion In dominantly inherited AD, soluble p‐tau181 and total tau changes in CSF appear to reflect disease processes that are distinct from the change in NFT pathology measured by tau PET. These results suggest the need for caution in extrapolating treatment related changes of soluble tau to those of NFT pathology.