Dataset Information

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

ABSTRACT:

Background

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.

Methods

Among 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.

Results

The 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.

Conclusions

Progressive 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.

SUBMITTER: Baek MS

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

REPOSITORIES: biostudies-literature

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Publications

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

Baek Min Seok MS Cho Hanna H Lee Hye Sun HS Lee Jae Hoon JH Ryu Young Hoon YH Lyoo Chul Hyoung CH

Alzheimer's research & therapy 20201031 1

<h4>Background</h4>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.<h4>Methods</h4>Among 272 individuals who underwent PET scans (<sup>18</sup>F-florbetaben for Aβ and <sup>18</sup>F-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 ...[more]

PMID: 33129364

Similar Datasets

Project description:BackgroundTo better assist with the design of future clinical trials for Alzheimer's disease (AD) and aid in our understanding of the disease's symptomatology, it is essential to clarify what roles β-amyloid (Aβ) plaques and tau tangles play in longitudinal tau accumulation inside and outside the medial temporal lobe (MTL) as well as how age, sex, apolipoprotein E (APOE) ε4 (APOE-ε4), and Klotho-VS heterozygosity (KL-VShet) modulate these relationships.MethodsWe divided the 325 Aβ PET-positive (A+) participants into two groups, A+/T- (N = 143) and A+/T+ (N = 182), based on the threshold (1.25) of the temporal meta-ROI 18F-flortaucipir (FTP) standardized uptake value ratio (SUVR). We then compared the baseline and slopes of A+/T- and A+/T+ individuals' Aβ plaques and temporal meta-ROI tau tangles with those of A-/T- cognitively unimpaired individuals (N = 162) without neurodegeneration. In addition, we looked into how baseline Aβ and tau may predict longitudinal tau increases and how age, sex, APOE-ε4, and KL-VShet affect these associations.ResultsIn entorhinal, amygdala, and parahippocampal (early tau-deposited regions of temporal meta-ROI), we found that baseline Aβ and tau deposition were positively linked to more rapid tau increases in A+/T- participants. However, in A+/T+ individuals, the longitudinal tau accumulation in fusiform, inferior temporal, and middle temporal cortices (late tau-deposited regions of temporal meta-ROI) was primarily predicted by the level of tau tangles. Furthermore, compared to older participants (age ≥ 65), younger individuals (age < 65) exhibited faster Aβ-dependent but slower tau-related tau accumulations. Additionally, compared to the KL-VShet- group, KL-VShet+ individuals showed a significantly lower rate of tau accumulation associated with baseline entorhinal tau in fusiform and inferior temporal regions.ConclusionThese findings offer novel perspectives to the design of AD clinical trials and aid in understanding the tau accumulation inside and outside MTL in AD. In particular, decreasing Aβ plaques might be adequate for A+/T- persons but may not be sufficient for A+/T+ individuals in preventing tau propagation and subsequent downstream pathological changes associated with tau.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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