Multicenter 18F-PI-2620 PET for In Vivo Braak Staging of Tau Pathology in Alzheimer’s Disease

Abstract

Tau aggregates accumulate in the Alzheimer’s disease (AD) brain according to the established Braak staging scheme and spread from transentorhinal over limbic regions to the neocortex. To impact the management of AD patients, an in vivo tool for tau Braak staging is needed. First-generation tau tracers have limited performance in detecting early stages of tau. Therefore, we tested the corresponding capability of the next-generation tau tracer, 18F-PI-2620. We analyzed 18F-PI-2620 multicenter PET data from 37 beta-amyloid-positive AD dementia patients and those from 26 healthy controls. We applied kinetic modeling of the 0–60 min p.i. PET data using MRTM2 with the lower cerebellum as the reference region to extract Braak stage-dependent distribution volume ratios, whereas controls were used to define Braak stage PET positivity thresholds. Stage-dependent PET positivity widely followed the Braak scheme (except Braak stage III) presenting descending frequency of PET positivity from Braak I (43%), II (38%), III (49%), IV (35%), V (30%) to VI (14%). A strictly hierarchical model was met by 64% of AD dementia cases. Nineteen percent showed a hippocampal sparing tauopathy pattern. Thus, we could assign 87% to the six-stage hierarchical Braak model including tauopathy variants. 18F-PI-2620 PET appears to be able to perform Braak tau staging of AD in vivo.

The hippocampal sparing subtype of Alzheimer’s disease assessed in neuropathology and in vivo tau positron emission tomography: a systematic review

“…Rullmann et al [ 33 ] also used the tau PET tracer 18F-PI-2620. The authors assessed 38 participants with AD dementia who were amyloid-beta positive.…”

The Use of Tau PET to Stage Alzheimer Disease According to the Braak Staging Framework

“…(A) Cases representative of each PET-based Braak stage included in Rullman et al. ( 27 ). Left column includes parametric 18 F-PI2620 PET images merged with standard MRI, whereas right column shows MRI images with atlas regions corresponding to each Braak stage ( 27 ).…”

“…( 27 ). Left column includes parametric 18 F-PI2620 PET images merged with standard MRI, whereas right column shows MRI images with atlas regions corresponding to each Braak stage ( 27 ). (B) Average 18 F-MK6240 SUV ratios across brains of participants in each PET-based Braak stage group included in Therriault et al.…”

Profiling and predicting distinct tau progression patterns: An unsupervised data‐driven approach to flortaucipir positron emission tomography

“…Other tau PET tracers, such as 18 F-MK-6240 and 18 F-PI-2620, have been shown to exhibit patterns that follow the AD Braak staging. 58,59 Thus, we expect the proposed tau progression profiling to be applicable to studies that use one of these tau radioligands or a combination of more than one tracer, if appropriate harmonization is performed. However, the different bind-…”