Effect of APOE ?4 genotype on amyloid-? and tau accumulation in Alzheimer's disease.

ABSTRACT: BACKGROUND:To assess the effects of apolipoprotein E (ApoE) ?4 genotype on amyloid-? (A?) and tau burden and their longitudinal changes in Alzheimer's disease (AD) spectrum. METHODS:Among 272 individuals who underwent PET scans (18F-florbetaben for A? and 18F-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? and tau burden between the ?4+ and ?4- groups. By using a linear mixed-effect model, we measured changes in SUVR in the ApoE ?4+ and ?4- groups. RESULTS:The ?4+ group showed greater baseline A? 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 ?4+ group. In A?+ individuals, baseline tau burden was greater in the medial temporal cortex, while A? burden was conversely greater in the ?4- group. Tau accumulation rate was higher in the ?4+ group in a small region in the lateral temporal cortex. The effect of ApoE ?4 on enhanced tau accumulation persisted even after adjusting for the global cortical A? burden. CONCLUSIONS:Progressive tau accumulation may be more prominent in ?4 carriers, particularly in the medial and lateral temporal cortices. ApoE ?4 allele has differential effects on the A? burden depending on the existing amyloidosis and may enhance vulnerability to progressive tau accumulation in the AD spectrum independent of A?.

SUBMITTER: Baek MS 

PROVIDER: S-EPMC7603688 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature