Plasma biomarkers identify brain ATN abnormalities in a dementia-free population-based cohort

Using the ATN framework, we evaluated the potential of plasma biomarkers to identify abnormal brain amyloid-beta (Aβ) positron emission tomography (PET), tau-PET and neurodegeneration in a socioeconomically disadvantaged population-based cohort.

Community-dwelling dementia-free (n=113, including 102 (91%) cognitively normal) participants underwent ATN neuroimaging and plasma biomarker assessments.

Plasma Aβ42/Aβ40, p-tau181, and p-tau217 showed significant associations with Aβ-PET status (adjusted odds ratio [AOR] of 1.74*10^-24, 1.47, and 3.43*10³ respectively [p-values<0.05]), with p-tau217 demonstrating the highest classification accuracy for Aβ-PET status (AUC=0.94). Plasma p-tau181 and p-tau217 showed significant associations with tau-PET status (AOR: 1.50 and 22.24, respectively, p-values<0.05), with comparable classification accuracies for tau-PET status (AUC=0.74 and 0.70, respectively). Only plasma NfL showed significant association with neurodegeneration based on cortical thickness (AOR=1.09, p-value<0.05).

Our findings highlight potential of plasma p-tau217 as a biomarker for brain Aβ and tau pathophysiology, p-tau181 for tau abnormalities, and NfL for neurodegeneration in the community.