Striatal tau burden is increased in APOE-e4+ mild cognitive impairment

Background The presence of β-amyloid (Aβ) extracellular plaques and hyper-phosphorylated tau neurofibrillary tangles characterize the pathology of Alzheimer’s disease (AD). The 18 F-AV1451 radioligand allows for assessment of tau burden in vivo using positron emission tomography (PET). However, this radioligand also binds with iron and this off-target binding may obscure tau deposition in iron rich gray matter structures in the striatum. Here we tested whether, when controlling for iron, striatal tau burden is higher in individuals at increased risk of developing AD (i.e., with mild cognitive impairment and high amyloid burden, Aβ+ MCI) relative to cognitively normal older adults. Methods In 38 Aβ+ MCI and 41 biomarker negative control participants (Aβ-, APOE ε4 non-carrier) from ADNI, we analyzed magnetic resonance imaging (MRI) measures sensitive to iron (quantitative susceptibility mapping) and PET measures of the 18 F-AV1451 radioligand binding sensitive to tau burden in high (bilateral putamen, globus pallidus, caudate nucleus) and low (thalamus, motor cortex) iron-containing gray matter regions. Results After controlling for tissue susceptibility, higher tau burden was found in the putamen and globus pallidus of Aβ+ MCI compared to the control group. Higher tau burden in the caudate nucleus of the Aβ+ MCI group was correlated with higher Alzheimer’s Disease Assessment Scale (ADAS) scores. Conclusions Controlling for iron allows for the assessment of tau burden in iron rich deep gray matter structures. Our findings suggest that Aβ burden increases the risk of developing AD-related tau pathology in the striatum and cognitive impairment.