Influence of medical conditions on the diagnostic accuracy of plasma p-tau217 and p-tau217/Aβ42.

Introduction: Blood-based biomarkers (BBMs) can enable early detection of brain amyloid beta (Aβ) pathology in cognitively unimpaired individuals. However, the extent to which common medical conditions affect biomarker performance remains unclear.

Methods: Participants (n = 348) included individuals without cognitive impairment. We studied how brain Aβ associated with BBMs (Aβ42/40, phosphorylated tau [p-tau] 181 and 217, p-tau217/Aβ42, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]) and optimal BBM thresholds for predicting brain Aβ positivity and whether they are obscured by the presence of common medical conditions.

Results: Plasma Aβ42/40, p-tau181, p-tau217, and GFAP, but not NfL, were significantly associated with brain Aβ. P-tau217/Aβ42 showed the best discriminative performance (area under the curve: 0.91). The strength of p-tau217-brain Aβ associations were obscured by diabetes and cardiovascular conditions.

Discussion: These results suggest BBMs may help detect early Aβ pathology but suggest caution in their use due to common medical conditions that could affect accuracy.

Highlights: Plasma Aβ42/40, p-tau181, p-tau217, and GFAP but not NfL showed significant associations with brain Aβ. BBMs were more strongly associated with the level of brain Aβ in those without diabetes and cardiovascular conditions. P-tau217/Aβ42 showed the best performance (AUC = 0.91) in discriminating Aβ presence with an optimal cut-off of >1.2, followed by p-tau217 at >0.46 pg/mL, with performance slightly improving when excluding participants with cardiovascular conditions.