Examining Iron‐related Off‐target Binding Effects of 18F‐AV1451 PET in the Cortex of Aβ+ Individuals

The 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 (F-18-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 F-18-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 (A beta+) individuals, 20 amyloid beta negative (A beta-) with MCI and 31 A beta- control participants. After controlling for iron, increased F-18-AV1451 PET uptake was found in the temporal lobe and hippocampus of A beta+ participants compared to A beta- MCI and control participants. Within the A beta+ group, significant correlations were seen between F-18-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 F-18-AV1451 ligand may not affect its sensitivity to A beta status or cognition in early-stage AD.