In‐vivo Braak Stage Distribution of Screened and Randomized Participants from Auτonomy, a Phase 2 Anti‐p‐tau Monoclonal Antibody Trial in Early Symptomatic Alzheimer’s Disease

Abstract

AbstractBackgroundTau PET is the gold standard for in‐vivo quantification of tau neurofibrillary tangles (NFT) which, along with amyloid plaques and neurodegeneration, constitute the pathological hallmarks of Alzheimer’s Disease (AD). The ongoing Autonomy trial (NCT04619420) enrolls participants presenting with mild cognitive impairment (MCI) or mild AD dementia who are tau PET positive. The Janssen plasma p217+tau assay is being used as a pre‐screen for eligibility to proceed to tau PET to reduce participant burden and improve screening efficiency. Using preliminary screening data available to date, we report on the in‐vivo PET‐based Braak stage distribution and compare the outcomes to published, histology‐based Braak staging.MethodNFT levels were quantified using 18F‐MK‐6240 SUVR in Braak Regions Of Interest (ROI)[1] using cerebellar gray as the reference region. In‐vivo Braak staging (Braakiv) was implemented following the approach by Biel et al.[2], with 18F‐flortaucipir to 18F‐MK‐6240 SUVR threshold conversion from Gogola et al.[3]. Participants with atypical[2] stages were reassigned to the Braak stage corresponding to the highest Braak ROI with average SUVR > 1.4. The screening results reported herein are from the first 355 participants with available biomarker screening data.ResultOf 355 screened participants, 90% were assigned to typical Braakiv stages. Of the 10% atypical stages, 94% were lacking elevated uptake in Braak 2 ROI. When using the coerced stage assignment, the average Braakiv stage was 3.7 across all screened participants and 3.6 in randomized participants (Figure 1). For the 221 randomized participants, 59% were Braakiv stage 4 or less, and 40% were Braakiv stage 3 or less.ConclusionIn early Alzheimer’s disease participants who were screened with tau PET in the ongoing Autonomy trial, the average Braakiv stage was consistent with the average histology‐based Braak stage in MCI patients of 3.57 [4]. These results further support the use of tau PET‐based in‐vivo staging[5] as a proxy for histology‐based Braak staging. [1] Schöll et al. Neuron 2016. [2] Biel, D., et al. Alz Res Therapy 2021. [3] Gogola A. et al. J Nucl Med. 2022. [4] Markesbery WR. J Alzheimers Dis. 2010. [5] Therriault, J. et al. Nat Aging 2022