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 (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.