Correlation between MK‐6240 tau‐PET and CSF tau, P‐tau and amyloid proteins

Abstract

AbstractBackgroundMK‐6240 is a promising second‐generation tau‐positron emission tomography (PET) tracer for evaluation of cerebral tauopathy in patients with and without cognitive impairment. To further validate the use of MK‐6240 in Memory Clinics, we aimed to evaluate the association between MK‐6240 PET results and well‐validated cerebrospinal fluid (CSF) tau and amyloid protein quantifications.MethodWe acquired MK‐6240 tau‐PET and 3D‐T1 MRI in 44 patients attending our Memory Clinic who accepted lumbar puncture. PET data were processed using PMOD 4.1 Neuro tool: we created three clusters of brain segments based on Braak pathological stages (1‐2; 3‐4 and 5‐6). Standardized uptake value ratio (SUVr) measures were calculated without partial volume correction for these three regions, using cerebellar grey matter as region of reference. SUVr measures in the three regions were correlated to CSF measures of total tau, phospho‐tau 181 (P‐tau) and amyloid (Aβ42) proteins. Linear regressions were calculated for each pair of data.ResultTable 1 provides the characteristics of the participants, as well as CSF and PET data. Fig. 1‐3 provides illustrative cases. We observed that SUVr significantly correlated with total (t‐tau) and P‐tau levels for each of the three Braak regions, but best correlated for the Braak 3‐4 region (t‐tau: r2=0.184; p=0.004 and p‐tau: r2=0.227; p=0.001, see Fig. 4). Only the Braak 1‐2 SUVr significantly correlated with CSF Aβ42 levels (r2=0.121; p=0.021, Fig. 4, line 3). The SUVr thresholds who best discriminate between CSF t‐tau positive and negative cases (based on our clinical threshold of 381pg/ml) were respectively: 1.54 SUVr (Braak1‐2), 1.35SUVr (Braak3‐4), 1.17SUVr (Braak5‐6).ConclusionAmyloid CSF levels only correlated with tau‐PET signal in the Braak 1‐2 region, suggesting an association between these two early pathological processes. In contrast, total and phosphorylated tau CSF levels best correlated with tau‐PET signal in the Braak 3‐4 region, suggesting that tau pathology has to reach the temporal neocortex prior to elevate a “global” tau‐measure such as the one measured in the CSF.