Examining iron‐related off‐target binding effects of 18F‐AV1451 PET in the cortex of Aβ+ individuals

Abstract

AbstractThe presence of neurofibrillary tangles containing hyper‐phosphorylated tau is a characteristic of Alzheimer's disease (AD) pathology. The positron emission tomography (PET) radioligand sensitive to tau neurofibrillary tangles (18F‐AV1451) also binds with iron. This off‐target binding effect may be enhanced in older adults on the AD spectrum, particularly those with amyloid‐positive biomarkers. Here, we examined group differences in 18F‐AV1451 PET after controlling for iron‐sensitive measures from magnetic resonance imaging (MRI) and its relationships to tissue microstructure and cognition in 40 amyloid beta positive (Aβ+) individuals, 20 amyloid beta negative (Aβ‐) with MCI and 31 Aβ‐ control participants. After controlling for iron, increased 18F‐AV1451 PET uptake was found in the temporal lobe and hippocampus of Aβ+ participants compared to Aβ‐ MCI and control participants. Within the Aβ+ group, significant correlations were seen between 18F‐AV1451 PET uptake and tissue microstructure and these correlations remained significant after controlling for iron. These findings indicate that off‐target binding of iron to the 18F‐AV1451 ligand may not affect its sensitivity to Aβ status or cognition in early‐stage AD.