Patterns of tau pathology identified with <sup>18</sup> F-MK-6240 PET imaging.

Overview

INTRODUCTION: Positron emission tomography (PET) imaging for neurofibrillary tau allows investigation of the in vivo spatiotemporal progression of Alzheimer's disease (AD) pathology. We evaluated the suitability of ¹⁸ F-MK-6240 in a clinical sample and determined the relationships among ¹⁸ F-MK-6240 binding, age, cognition, and cerebrospinal fluid (CSF)-based AD biomarkers. METHODS: Participants (n = 101, 72 ± 9 years, 52% women) underwent amyloid PET, tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Twenty-one participants had lumbar puncture for CSF measurement of amyloid beta (Aβ)₄₂ , tau, and phosphorylated tau (p-tau). RESULTS: ¹⁸ F-MK-6240 recapitulated Braak staging and correlated with CSF tau and p-tau, normalized to Aβ₄₂ . ¹⁸ F-MK-6240 negatively correlated with age across Braak regions in amyloid-positive participants, consistent with greater tau pathology in earlier onset AD. Domain-specific, regional patterns of ¹⁸ F-MK-6240 binding were associated with reduced memory, executive, and language performance, but only in amyloid-positive participants. DISCUSSION: ¹⁸ F-MK-6240 can approximate Braak staging across the AD continuum and provide region-dependent insights into biomarker-based AD models.