Multicenter F-18-PI-2620 PET for in vivo Braak staging of tau pathology in Alzheimer’s disease

Ziel/Aim Tau aggregates accumulate, in the Alzheimer Disease (AD) brain, following the well-established Braak staging scheme, propagating from transentorhinal over limbic regions into the neocortex. To impact AD patient management, an in vivo tool for tau Braak staging is desired. The early-generation tau tracers have limited performance for detecting early tau stages. Thus, we tested the respective ability of the next-generation tau tracer F-18-PI-2620.

Methodik/Methods We analyzed F-18-PI-2620 PET data of beta-amyloid positive 36 AD dementia patients (70 ± 9 years, 19 females, MMSE scores: 20 ± 6) and those of 19 healthy controls (63 ± 10 years, 10 females, MMSE scores: 29 ± 1). The data were acquired in four different centers (Leipzig, Germany; Melbourne, Australia; Munich, Germany; New Haven, USA). We applied kinetic modeling of 0-60min p.i. PET data using MRTM2 with lower cerebellum as reference region. We used the tau Braak staging atlas of Schwarz et al. 2016 to extract respective DVRs. Controls were used to define stage-dependent PET positivity (>mv+2.5sd). In addition, we condensed the six-stage model data into an established four-class model (0, I+II, III+IV and V+VI).

Ergebnisse/Results Stage-dependent PET positivity widely followed the Braak scheme (except for Braak stage III). The PET positivity frequency declined from Braak I (42 %), II (33 %), III (58 %), IV (31 %), V (22 %) to VI (19 %). A hierarchical model (allowing a stage>I to be defines as positive only in case the lower stage(s) is/are positive) was fulfilled by 56 % AD dementia cases for the six-stage model, while this was the case in 78 % of the cases for the four-class Braak staging model. Six cases (17 %) showed a “hippocampal sparing” tauopathy pattern.

Schlussfolgerungen/Conclusions F-18-PI-2620 PET seems to be able to perform Braak tau staging of AD in vivo. The results should benefit from further analysis like partial volume effect correction.

Publication History

Article published online:
08 April 2021

• Literatur/References

• Adam J Schwar z, Peng Yu, Bradley B Miller, Sergey Shcherbinin, James Dickson, Michael Navitsky, Abhinay D Joshi, Michael D Devous Sr, Mark S Mintun. Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages. Brain 2016 May; 139 (Pt 5): 1539-50. DOI: 10.1093/brain/aww023.