Relationship between amyloid and tau levels and its impact on tau spreading

Purpose Previous studies have shown that A beta-amyloid (A beta) likely promotes tau to spread beyond the medial temporal lobe. However, the A beta levels necessary for tau to spread in the neocortex is still unclear. Methods Four hundred sixty-six participants underwent tau imaging with [18F]MK6420 and A beta imaging with [F-18]NAV4694. A beta scans were quantified on the Centiloid (CL) scale with a cut-off of 25 CL for abnormal levels of A beta (A+). Tau scans were quantified in three regions of interest (ROI) (mesial temporal (Me); temporoparietal neocortex (Te); and rest of neocortex (R)) and four mesial temporal region (entorhinal cortex, amygdala, hippocampus, and parahippocampus). Regional tau thresholds were established as the 95%ile of the cognitively unimpaired A- subjects. The prevalence of abnormal tau levels (T+) along the Centiloid continuum was determined. Results The plots of prevalence of T+ show earlier and greater increase along the Centiloid continuum in the medial temporal area compared to neocortex. Prevalence of T+ was low but associated with A beta level between 10 and 40 CL reaching 23% in Me, 15% in Te, and 11% in R. Between 40 and 70 CL, the prevalence of T+ subjects per CL increased fourfold faster and at 70 CL was 64% in Me, 51% in Te, and 37% in R. In cognitively unimpaired, there were no T+ in R below 50 CL. The highest prevalence of T+ were found in the entorhinal cortex, reaching 40% at 40 CL and 80% at 60 CL. Conclusion Outside the entorhinal cortex, abnormal levels of cortical tau on PET are rarely found with A beta below 40 CL. Above 40 CL prevalence of T+ accelerates in all areas. Moderate A beta levels are required before abnormal neocortical tau becomes detectable.

Automated summary

The study found that Aβ levels between 10 and 40 CL are associated with spreading of tau protein in different brain regions, and abnormal levels of tau protein in the neocortex require Aβ levels above 40 CL. The highest prevalence of abnormal tau protein was found in the entorhinal cortex.