Plasma Phosphorylated Tau 217 and Aβ42/40 to Predict Early Brain Aβ Accumulation in People Without Cognitive Impairment

• DOI: 10.1001/jamaneurol.2024.2619
• Publication Date: 2024-07-28T19:30:28Z
• Authors: Shorena Janelidze; Nicolas R. Barthé...; Gemma Salvadó; Suzanne E. Schindler; Sebastian Palmqvist; Niklas Mattsson-C...; Joel B. Braunstein; Vitaliy Ovod; James G. Bollinger; Yingxin He; Yan Li; Cyrus A. Raji; John C. Morris; David M. Holtzman; Nicholas J. Ashton; Kaj Blennow; Erik Stomrud; Randall J. Bateman; Oskar Hansson
• Keywords: Longitudinal Study; Cognitive Decline

Importance Phase 3 trials of successful antiamyloid therapies in Alzheimer disease (AD) have demonstrated improved clinical efficacy people with less severe disease. Plasma biomarkers will be essential for efficient screening participants future primary prevention testing cognitively unimpaired (CU) individuals initially low brain β-amyloid (Aβ) levels who are at high risk accumulating Aβ. Objective To investigate if combining plasma could useful predicting subsequent development Aβ pathology CU subthreshold (defined as <40 Centiloids) baseline. Design, Setting, and Participants This was a longitudinal study including Swedish BioFINDER-2 (enrollment 2017-2022) replication 2 independent cohorts, the Knight Disease Research Center (Knight ADRC; enrollment 1988 2019) BioFINDER-1 2009-2015). Included analysis convenience sample baseline phosphorylated tau 217 (p-tau217) Aβ42/40 assessments positron emission tomography (Aβ-PET) or cerebrospinal fluid (CSF) Aβ42/40. Data were analyzed between April 2023 May 2024. Exposures Baseline Aβ42/40, p-tau217, ratio p-tau217 to nonphosphorylated (%p-tau217), p-tau231, glial fibrillary acidic protein (GFAP). Main Outcomes Measures Cross-sectional PET CSF measures pathology. Results included 495 (BioFINDER-2), 283 ADRC), 205 (BioFINDER-1) participants. In BioFINDER-2, mean (SD) age 65.7 (14.4) 261 females (52.7%). When detecting abnormal Aβ-status, combination %p-tau217 showed better performance (area under curve = 0.949; 95% CI, 0.929-0.970; P <.02) than individual biomarkers. Aβ-PET, significantly associated Aβ-PET (n 384) increases over time 224). Associations their interaction (%p-tau217: β 2.77; 1.84-3.70; Aβ42/40: −1.64; −2.53 −0.75; × −2.14; −2.79 −1.49; < .001) 0.67; 0.48-0.87; −0.33; −0.51 −0.15; −0.31; −0.44 −0.18; also significant models predictors. Similarly, independently ADRC 0.71; 0.26-1.16; .002; −0.74; −1.26 −0.22; .006) (p-tau217: −0.0003; −0.0004 −0.0001; .01; 0.0004; 0.0002-0.0006; p-tau231 GFAP did not provide any clear value. Conclusions Relevance this cohort suggest that p-tau217and early stages accumulation. These might thus facilitate trials.