Associations of Age and Sex with Levels of Tau PET in Screened Participants from Auτonomy, a Phase 2 Anti‐p‐tau Monoclonal Antibody Trial in Early Symptomatic Alzheimer’s Disease

Abstract

AbstractBackgroundThe ongoing Autonomy trial (NCT04619420) enrolls participants presenting with mild cognitive impairment (MCI) or mild AD dementia with a CDR Global Score of 0.5 and who are tau PET positive. The Janssen plasma p217+tau assay is 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 associations of age and sex with tau PET, a biomarker for neurofibrillary tangle (NFT) burden, and with plasma p217+tau levels.Method18F‐MK6240 Tau PET SUVRs for 355 screened participants (180 female) were quantified in Braak Regions Of Interest (ROI)[1] 1 through 6 using cerebellar gray as reference region. Associations were analyzed using a linear model of regional SUVR as a function of age and sex. Additionally, models of association for plasma p217+tau in log(pg/ml) were considered.ResultAge at baseline was not different (p>0.5) for female (70.84 y) versus male (70.49 y) participants. For Braak 3 ROI, tau PET SUVRs showed significant negative association for age (R2partial = 16%, p<10‐14), and increased levels in females (R2partial = 2%, p<0.01). The results were qualitatively similar across Braak ROIs 1 through 4. For Braak ROIs 5, and 6, the effect of sex was no longer significant, although the trend remained in a consistent direction. For plasma p217+tau, we found significant negative association for age (R2partial = 7%, p<10‐6) and a trend for higher levels in female participants (R2partial = 1%, p = 0.05).ConclusionIn early Alzheimer’s disease participants who were screened with tau PET for the ongoing Autonomy trial, higher SUVR was observed for younger versus older participants and in females versus males. The effect of age is likely due to the cohort’s cognitive uniformity whereby in younger participants, a higher tau burden as measured by PET is required for the same level of impairment as older participants[2]. The increased tau PET NFT levels observed in female participants is consistent with findings by Edwards et al. [3]. Associations of similar directions were also observed for plasma p217+tau. [1] Schöll et al., Neuron 2016. [2] Jack et al., Brain 2018. [3] Edwards L et al., Neurobiology of Aging 2021