Leuzy A, Smith R, Cullen NC, et al. - Findings indicate that plasma p-tau217 (tau phosphorylated at threonine-217) with tau positron emission tomography (PET) could be optimal for enrichment in preclinical and prodromal Alzheimer disease (AD), in trials using tau PET as the outcome. However, plasma p-tau217 was most crucial in preclinical AD, while tau PET showed more importance in prodromal AD.

• This cohort study included 343 participants including amyloid-β (Aβ)–positive persons who were cognitively unimpaired (CU) or had mild cognitive impairment (MCI), to determine the biomarkers that best predict longitudinal tau accumulation at different clinical stages of AD.

• Five regions of interest (stages) were discovered using clustering/event-based modeling–based approach.

• The largest annual increase in tau PET standardized uptake value ratio (SUVR) among Aβ-positive CU individuals was evident in stage I (entorhinal cortex, hippocampus, and amygdala; 4.04%).

• In Aβ-positive persons with MCI and with AD dementia, the greatest increases were observed in stages II (temporal cortical regions; 4.45%) and IV (certain frontal regions; 5.22%), respectively.

• Modest change, in Aβ-negative CU people and those with MCI, was evident in stage I (1.38% and 1.80%, respectively).

• In Aβ-positive cases with MCI, plasma p-tau217 and tau PET were identified to be significantly related to longitudinal tau PET in stage II.

• A power analysis revealed sample size reductions due to plasma phosphorylated tau217 with tau PET at baseline in stage I and II, respectively.