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Relationship between amyloid and tau levels and its impact on tau spreading
Author(s) -
Dore Vincent,
Krishnadas Natasha,
Bourgeat Pierrick,
Huang Kun,
Li Shenpeng,
Burnham Samantha C,
Masters Colin L,
Fripp Jurgen,
Villemagne Victor L,
Rowe Christopher C
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.055714
Subject(s) - neocortex , entorhinal cortex , temporal lobe , temporal cortex , amygdala , cortex (anatomy) , hippocampus , neuroscience , tau pathology , medicine , psychology , alzheimer's disease , disease , epilepsy
Background Previous studies have shown that Aß‐amyloid (Aß) likely promotes tau to spread beyond the medial temporal lobe. However, the Aß levels necessary for tau to spread in the neocortex is still unclear. Method 466 participants underwent tau imaging with [ 18 F]MK6420 and Aß imaging with [ 18 F]NAV4694 (Fig. 1). Aß scans were quantified on the Centiloid (CL) scale with a cut‐off of 25CL for abnormal levels of Aß (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) using the cerebellar cortex as reference region. 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. Result The plots of prevalence of T+ (Fig. 2) 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 Aß level between 10‐40 CL reaching 23% in Me, 15% in Te and 11% in R. Between 40‐70 CL, the prevalence of T+ subjects per CL increased four‐fold faster and at 70 CL was 64% in Me, 51% in Te and 37% in R. In cognitively unimpaired (Fig. 3), there were no T+ in R below 50 CL. The highest prevalence of T+ was 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 Aß levels below 40 CL. Above 40 CL prevalence of T+ accelerates in all areas. Moderate Aß levels are required before neocortical tau becomes detectable.