Effect of APOE ε4 genotype on amyloid-β and tau accumulation in Alzheimer's disease

Background To assess the effects of apolipoprotein E (ApoE) epsilon 4 genotype on amyloid-beta (A beta) and tau burden and their longitudinal changes in Alzheimer's disease (AD) spectrum. Methods Among 272 individuals who underwent PET scans (F-18-florbetaben for A beta and F-18-flortaucipir for tau) and ApoE genotyping, 187 individuals completed 2-year follow-up PET scans. After correcting for the partial volume effect, we compared the standardized uptake value ratio (SUVR) for A beta and tau burden between the epsilon 4+ and epsilon 4- groups. By using a linear mixed-effect model, we measured changes in SUVR in the ApoE epsilon 4+ and epsilon 4- groups. Results The epsilon 4+ group showed greater baseline A beta burden in the diffuse cortical regions and greater tau burden in the lateral, and medial temporal, cingulate, and insula cortices. Tau accumulation rate was higher in the parietal, occipital, lateral, and medial temporal cortices in the epsilon 4+ group. In A beta+ individuals, baseline tau burden was greater in the medial temporal cortex, while A beta burden was conversely greater in the epsilon 4- group. Tau accumulation rate was higher in the epsilon 4+ group in a small region in the lateral temporal cortex. The effect of ApoE epsilon 4 on enhanced tau accumulation persisted even after adjusting for the global cortical A beta burden. Conclusions Progressive tau accumulation may be more prominent in epsilon 4 carriers, particularly in the medial and lateral temporal cortices. ApoE epsilon 4 allele has differential effects on the A beta burden depending on the existing amyloidosis and may enhance vulnerability to progressive tau accumulation in the AD spectrum independent of A beta.