Associations of the A/T/N profiles in PET, CSF, and plasma biomarkers with Alzheimer's disease neuropathology at autopsy

Abstract INTRODUCTION To examine the extent to which positron emission tomography (PET)‐, cerebrospinal fluid (CSF)‐, and plasma‐related amyloid‐β/tau/neurodegeneration (A/T/N) biomarkers are associated with Alzheimer's disease (AD) neuropathology at autopsy. METHODS A total of 100 participants who respectively underwent antemortem biomarker measurements and postmortem neuropathology were included in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We examined the associations of PET‐, CSF‐, and plasma‐related A/T/N biomarkers in combinations or alone with AD neuropathological changes (ADNC). RESULTS PET‐ and CSF‐related A/T/N biomarkers in combination showed high concordance with the ADNC stage and alone showed high accuracy in discriminating autopsy‐confirmed AD. However, the plasma‐related A/T/N biomarkers alone showed better discriminative performance only when combined with apolipoprotein E ( APO)E ε4 genotype. DISCUSSION This study supports that PET‐ and CSF‐related A/T/N profiles can be used to predict accurately the stages of AD neuropathology. For diagnostic settings, PET‐, CSF‐, and plasma‐related A/T/N biomarkers are all useful diagnostic tools to detect the presence of AD neuropathology. HIGHLIGHTS PET‐ and CSF‐related A/T/N biomarkers in combination can accurately predict the specific stages of AD neuropathology. PET‐ and CSF‐related A/T/N biomarkers alone may serve as a precise diagnostic tool for detecting AD neuropathology at autopsy. Plasma‐related A/T/N biomarkers may need combined risk factors when used as a diagnostic tool. Aβ PET and CSF p‐tau181/Aβ42 were most consistent with Aβ pathology, while tau PET and CSF p‐tau181/Aβ42 were most consistent with tau pathology.