O3-02-02: amyloid pet, tau pet, and mri measurements in cognitively unimpaired persons with two, one, and no copies of the apoe4 allele

We recently characterized relationships between tau PET measurements and apolipoprotein E4 (APOE4) gene dose in cognitively unimpaired late middle-aged and older adults and the extent to which these relationships are associated with age, amyloid-β (Aβ) positivity, and long-term verbal memory decline. We now extend those findings to a larger number of research participants, incorporate MRI measurements of cortical atrophy and provide new information about the AD biomarker classification of those with two, one, and no APOE4 alleles using the (Aβ/tau[neurodegeneration]) “AT(N)” framework. Pittsburgh Compound-B (PiB) PET, flortaucipir PET, and T1-weighted volumetric MRI were used to assess fibrillar Ab burden, paired helical tau burden, and cortical atrophy in 165 participants, ages 47-86, in the Arizona APOE Cohort Study and Mayo Clinic Study of Aging, including 26 APOE4 homozygotes, 48 heterozygotes, and 91 non-carriers matched for age, sex, and education. SPM12 and previously described regions-of-interest (ROIs) were used to characterize composite cortical-to-cerebellar PiB standard uptake value ratios (SUVRs) and entorhinal cortex, inferior temporal cortex, and composite cortical-to-cerebellar flortaucipir SUVRs; FreeSurfer and previously described cortical ROIs were used to provide a composite measure of cortical thickness. Previously described composite PiB SUVR≥1.42, flortaucipir SUVR≥1.23, and cortical thickness ≤2.67mm thresholds were used to classify participants using the AT(N) framework. 38%, 35%, and 12% of the APOE4 homozygotes, heterozygotes, and non-carriers had a “positive” PiB PET scan. Compared to non-carriers, the homozygotes and heterozygotes had higher PiB SUVRs (p<0.01). They also had higher entorhinal flortaucipir SUVRs and greater associations between composite flortaucipir SUVRs and age, findings that were solely attributable to those carriers with a positive PiB PET scan (p<0.05). We will discuss these and other findings, including the percentages of each AT(N) classifications and the extent to which downstream biomarkers are influenced by Ab positivity, age, and their interaction with two, one or no APOE4 alleles. This study provides new information about AT(N) measurements and classifications in an unusually large number of cognitively unimpaired persons at three levels of genetic risk for late-onset AD. Tau pathology is preferentially affected in unimpaired APOE4 carriers with a positive Aβ PET scan.