Spread of tau deposits: can we trust in vivo findings?

Herholz, Karl

doi:10.1093/brain/awx340

Cited by 2 publications

(1 citation statement)

References 8 publications

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“…In vivo studies using early-generation tau tracers allowed for the first time to visualize anatomical distribution of tau directly in the living human brain [6,7]. Unfortunately, off-target binding, a key problem of those first-generation tau tracers, restrained the performance in detecting early tau stages [8][9][10][11]. Second-generation tau tracer overcome those drawbacks [12,13] and should be tested if they can recapitulate early and late Braak stages in vivo.…”

Section: Introductionmentioning

confidence: 99%

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

Rullmann¹,

Brendel²,

Schroeter³

et al. 2022

Biomolecules

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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.

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