Abstract
INTRODUCTION: We investigated the presence of neurofibrillary tangles (NFT) and their association with amyloid plaques and fluid biomarkers of Alzheimer's disease (AD) in cognitively unimpaired individuals (CU). METHODS: Ninety-nine CU individuals from the ALFA+ cohort underwent tau PET using (18) F-RO-948, amyloid PET, MRI, cognitive assessments, and (CSF)/plasma biomarkers. Tau PET SUVRs calculated in Braak regions, and associations with AD biomarkers were assessed. Thresholds for positivity were derived, and ROC analysis evaluated biomarker accuracy in predicting tau PET positivity. RESULTS: Nine cases were Braak-I/II positive, five Braak-III/IV, and one Braak-V/VI. For CSF biomarkers, the strongest associations with Braak-I/II reached r=0.58 [95%CI:0.26-0.79, p<0.001, CSF ptau217] and, for plasma, r=0.25 [95%CI:0.03-0.45, p=0.01, plasma ptau181/Aβ42], but showed low PPVs [0.09-0.33] for Braak-I/II positivity. DISCUSSION: (18) F-RO-948 PET was capable of detecting positive cases in the earliest preclinical AD stages. The studied fluid biomarkers alone showed limited accuracy for screening CU individuals for tau PET positivity.