Abstract
BackgroundTo assess the effects of apolipoprotein E (ApoE) ε4 genotype on amyloid-β (Aβ) and tau burden and their longitudinal changes in Alzheimer’s disease (AD) spectrum.MethodsAmong 272 individuals who underwent PET scans (18F-florbetaben for Aβ 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 Aβ and tau burden between the ε4+ and ε4− groups. By using a linear mixed-effect model, we measured changes in SUVR in the ApoE ε4+ and ε4− groups.ResultsThe ε4+ group showed greater baseline Aβ 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 ε4+ group. In Aβ+ individuals, baseline tau burden was greater in the medial temporal cortex, while Aβ burden was conversely greater in the ε4− group. Tau accumulation rate was higher in the ε4+ group in a small region in the lateral temporal cortex. The effect of ApoE ε4 on enhanced tau accumulation persisted even after adjusting for the global cortical Aβ burden.ConclusionsProgressive tau accumulation may be more prominent in ε4 carriers, particularly in the medial and lateral temporal cortices. ApoE ε4 allele has differential effects on the Aβ burden depending on the existing amyloidosis and may enhance vulnerability to progressive tau accumulation in the AD spectrum independent of Aβ.
Highlights
To assess the effects of apolipoprotein E (ApoE) ε4 genotype on amyloid-β (Aβ) and tau burden and their longitudinal changes in Alzheimer’s disease (AD) spectrum
A recent 18F-flortaucipir positron emission tomography (PET) study demonstrated that ApoE ε4 had an Aβindependent effect on the increase in the tau load in the entorhinal cortex and hippocampus [16], while the other studies found this effect was associated with the global Aβ burden [17] or even greater tau burden in the prodromal AD and AD dementia patients without the ε4 allele, in the parietal cortex, than in patients who carried the ε4 allele [18]
We investigated the effects of the ε4 allele on regional Aβ and tau burden and their longitudinal changes in cognitively unimpaired (CU) individuals, mild cognitive impairment (MCI) patients, and AD patients
Summary
To assess the effects of apolipoprotein E (ApoE) ε4 genotype on amyloid-β (Aβ) and tau burden and their longitudinal changes in Alzheimer’s disease (AD) spectrum. The apolipoprotein E (ApoE) gene encodes a 35-kDa extracellular lipid and cholesterol carrier glycoprotein, and its ε4 allele is a major genetic risk factor for sporadic AD [1, 3]. The presence of this allele increases the risk of AD in a dose-dependent manner and lowers the age at Greater amounts of Aβ burden were observed in ε4 carriers than in non-carriers in previous postmortem and 11C-Pittsburgh compound B (PIB) positron emission tomography (PET) studies [6,7,8]. A recent 18F-flortaucipir PET study demonstrated that ApoE ε4 had an Aβindependent effect on the increase in the tau load in the entorhinal cortex and hippocampus [16], while the other studies found this effect was associated with the global Aβ burden [17] or even greater tau burden in the prodromal AD and AD dementia patients without the ε4 allele, in the parietal cortex, than in patients who carried the ε4 allele [18]
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